The Briton headed title rival and Mercedes team-mate Nico Rosberg by 0.079 seconds in the second session at Abu Dhabi's Yas Marina track, having been 0.374secs quicker in first practice on Friday.
Hamilton is 12 points behind the German and has to win the race and hope his Mercedes team-mate finishes lower than third if he is to win the championship.
Ferrari's Sebastian Vettel was only 0.269secs slower than Hamilton in third place, and a similar margin ahead of Red Bull's Max Verstappen and Daniel Ricciardo.
Hamilton's best hope for the championship is that other cars get between him and Rosberg in the race.
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And there was some encouragement on that front, with strong long runs from the Red Bulls during the second part of the session when the teams run the cars full of fuel in preparation for the race.
Ricciardo set the quickest average time over his race run on the ultra-soft tyre on which most are likely to start the race.
Hamilton was quickest on the soft tyre later in the session, but both Ricciardo and Verstappen were marginally faster than Rosberg.
However, Friday runs can be misleading indicators of form, and Mercedes always tend to take a step ahead on Saturdays when they turn their engines up into a higher-performance mode.
Ferrari's form was hard to judge as Vettel and Raikkonen did their race runs out of sync with the others in terms of tyre choice and the German stopped out on track late in the session with what he suspected was a gearbox failure.
Williams' Valtteri Bottas was seventh fastest ahead of the Force Indias of Sergio Perez and Nico Hulkenberg and the second Williams of Felipe Massa.
McLaren's Jenson Button was 12th fastest, one place but 0.457secs behind team-mate Fernando Alonso.
Toro Rosso had a difficult session, stopping all their running after Daniil Kvyat had a spin caused by his second puncture of the day after just four laps.
The car's suspension is fouling the left rear wheel under load and the team stopped all running while they fixed the problem.
Abu Dhabi Grand Prix second practice results
Abu Dhabi Grand Prix coverage page
Lewis Hamilton was fastest in both practice sessions at the start of the weekend that will decide the 2016 Formula 1 World Championship.