The younger Henderson opened his account for the Easter Road side after joining from Celtic in January as the visitors edged a close encounter at the SMiSA Stadium in the first post-split fixture.
Henderson collected Harry Clarke's pass before finishing well past Buddies 'keeper Jak Alnwick, as Easter Road interim boss David Gray got his second temporary spell in charge off to a winning start with three points in Paisley.
Brother Liam helped Empoli to their first Serie A victory since December 12 as the Tuscan outfit scored three goals in the final ten minutes to stun Luciano Spalletti's side, who had taken a two-goal lead eight minutes into the second half courtesy of strikes either side of the interval from Dries Mertens and Lorenzo Insigne.
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But Henderson, a 61st-minute replacement for Filippo Bandinelli, pulled one back on 80 minutes and Internazionale loanee Andrea Pinamonti levelled on 83 minutes before scoring the winner three minutes from time.
Napoli next face Sassuolo at home on Saturday with Empoli travelling to face Torino. Napoli stay third in the league, four ahead of Juventus who face Sassuolo tonight at the Stadio Città del Tricolore and five behind Inter, who travel to face Aaron Hickey's Bologna on Wednesday night.
Hickey, meanwhile, scored his fifth goal of the season as Bologna drew 2-2 with Udinese at the weekend.