The Argentine hitman ended a lean spell in front of goal in emphatic style. His treble helped Napoli to a third victory over Lazio in all competitions this season. Dries Mertens had earlier cancelled out Senad Lulic's opener before Lorik Cana saw red for two bookable offences. Ogenyi Onazi ensured a frantic finale when he reduced the arrears until Higuain sealed the game. Napoli have all but confirmed third place, while Lazio lose ground in the race for a Europa League place.
Injured pair Christian Maggio and Juan Zuniga missed out for the home side and Rafa Benitez opted to rest Jose Callejon. Valon Behrami and Goran Pandev were both given starts against their former club. Lorenzo Insigne was handed the captain's armband.
Edy Reja returned to the club he took from Serie C1 back to the top flight, but the Biancocelesti had a long list of absentees. Federico Marchetti, Andre Dias, Giuseppe Biava, Alvaro Gonzalez, Ederson, Miroslav Klose and Keita Balde were all injured, while Lucas Biglia was suspended. Cristian Ledesma returned after a two-game ban and Stefano Mauri was used as a makeshift striker, flanked by Felipe Anderson and Antonio Candreva.
The Lazio defence stood firm to repel Napoli inside the opening 10 minutes. Pandev sent Insigne clear, but the winger failed to look up and see Higuain in the box, opting to go alone and send his effort into the side netting.
Cana risked a red card when he brought Higuain down. The Albanian only just avoided being the last man and was given a caution. Mertens sent the resulting free kick into the Lazio wall.
The visitors finally came to life after 15 minutes. Candreva picked out Mauri, but the Lazio captain's first-time effort curled wide. Anderson couldn't keep his side's next effort down and blasted into the stands. It didn't matter, as Lazio opened the scoring on 21 minutes. Lulic expertly turned Raul Albiol in the box and beat Pepe Reina with a low finish to claim his second goal in as many matches.
The game was end-to-end. Etrit Berisha kept out Higuain, while Reina blocked Anderson's toepoke with his feet, after the Brazilian turned Mertens in the box.
Lazio failed to clear their area properly and Behrami sent an effort over the bar. Insigne also went close with a half volley. At the other end, Onazi picked up Lulic's lay off and drilled his shot the wrong side of the post.
Napoli drew level four minutes before halftime with an absolute screamer. Mertens cut inside and hit a thunderous strike from the edge of the box, which flew past Berisha as it zipped into the top corner.
The Belgian continued to torment the Lazio defence, playing a dangerous ball across the face of goal which went unclaimed. Mertens and Ledesma were both booked on the stroke of halftime for instigating a scuffle. Mertens has hit the yellow card limit and will miss Napoli's game at Udinese next weekend.
Lazio started the second half in the worst way possible. Just three minutes after the restart, Cana brought down Mertens in the area after the midfielder played a one-two with Higuain. The referee awarded a penalty and gave Cana a second booking. Higuain stepped up and put his spot kick beyond the dive of Berisha to net his first goal in five games.
Higuain had re-discovered his scoring touch and grabbed another goal midway through the second half. The forward headed Insigne's high ball past Diego Novaretti and buried a shot past Berisha into the far corner.
Berisha stopped the game from becoming a rout, performing a quick double save to deny Higuain his hat trick, then Callejon from putting in the rebound. Lazio retreated and went more defensive to try and keep their hosts at bay. Helder Postiga mustered a shot from distance which was easily gathered by Reina. Onazi saw a similar effort meet the same fate.
Onazi handed Lazio a lifeline eight minutes from the end. The Nigerian sprinted onto a pass and muscled Miguel Britos off the ball, before slotting the ball through Reina's legs and following through to ensure the ball found the back of the net.
Lazio pushed for an unlikely equaliser. Luis Cavanda flashed a shot across the box, Postiga had an effort correctly ruled out for offside and Michael Ciani saw a header easily caught. Napoli exploited the gaps at the back to add a fourth in stoppage time. Novaretti was beaten to a high ball by Higuain, who ran on and chipped the ball over Berisha to claim his 17th goal of the season.
Napoli: Reina; Henrique, Albiol, (Fernandez 46) Britos, Ghoulam; Jorginho, (Mesto 83) Behrami; Mertens, (Callejon 65) Pandev, Insigne; Higuain
Goals: Mertens 41, Higuain pen 49, 67, 90+4
Lazio: Berisha; Konko, Ciani, Cana, Radu; Onazi, Ledesma, Lulic; (Cavanda 74) Candreva, Mauri, (Postiga 56) Felipe Anderson (Novaretti 63)
Goals: Lulic 21, Onazi 82
Sent off: Cana 48