The Sixers, who are 2-0 to start the BBL season, chased down the Hurricanes' 8-135 with four balls to spare in Launceston on Monday night.
Hughes top scored with an unbeaten 60 from 50 balls after replacing Steve Smith who left the squad ahead of Thursday's first Test against Pakistan.
He shared a 47-run partnership with Moises Henriques (20 from 24) to iron out a decent chunk of the chase.
Jordan Silk chipped in with 23 before falling in the second last over.
With Sydney needing seven from six deliveries, Hughes put the result beyond doubt with a towering leg-side six off Nathan Ellis.
Riley Meredith pulled up after bowling nine balls on his return to action after three months out. (Linda Higginson/AAP PHOTOS)
Tom Curran then iced the game with a boundary through the covers.
Meredith pulled up sore gesturing to his side halfway through the third over of the chase after sending down a 152km/h delivery.
It was his first game back at domestic level since suffering a side strain in a one-day cup game for Tasmania in September.
Hurricanes coach Jeff Vaughan told Channel 7 Meredith would have scans on Tuesday.
Earlier, Hobart opener Caleb Jewell (42 from 24) got his side off to a flyer before the wheels fell off after the powerplay.
Curran (3-19) started the damage when he had Jewell caught at mid-off in the sixth over.
Fellow quick Ben Dwarshuis (2-21) then picked up England import Sam Hain and Australia representative Tim David for single figures in his first over.
Young allrounder Jack Edwards got in on the action, with wicketkeeper Josh Philippe snaffling a one-handed diving catch at full stretch to grab the edge of Ben McDermott.
Edwards, who finished with 2-18 from four overs, had only bowled one over in his 30 previous BBL matches.
Hobart fell to 5-69 in the ninth over before imports Chris Jordan (16 from 21) and Corey Anderson (17 from 27) stemmed the bleeding.
New Zealand's Anderson was the pick of Hobart's bowlers with 2-10.
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