Hufanga had two tries in each half as the Broncos ventured north and spoiled the Cowboys' maiden game at Queensland Country Bank Stadium.
Her achievement follows in the footsteps of Taleena Simon, who achieved the four-try feat for the Sydney Roosters in 2018, and sparked Brisbane's first win of 2023 after losses to the Sydney Roosters and Gold Coast.
The visitors raced out to a three-try lead within 16 minutes on Saturday as the Cowboys struggled to gain a foothold early in the contest.
Ali Brigginshaw's grubber behind the line split two defenders and Tazmin Gray grabbed the opener, before some direct play by Brisbane's middle forwards had the Cowboys' shot on the left edge as Hufanga scored their second six minutes later.
Brisbane's halves combined to put Toni Hunt over for a career-first try to make it 14-0.
The deficit seemed to shock North Queensland into gear, with the hosts dominating the remainder of the half with their first points coming through Shellie Long off a scrum play.
Kirra Dibb's solo-effort almost narrowed the margin further but her 'try' was overturned on review due to a knock-on.
Hufanga crossed for a first-half double off the back of a penalty but the Cowboys scored on the stroke of halftime through April Ngatunpuna to trail 18-12 heading into the sheds.
Within five minutes of the restart, though, Hufanga went bang-bang as Brisbane's lead ballooned out to 28-12.
Lauren Dam crossed 10 minutes from time before Brigginshaw - who was placed on report for a tip-tackle in the first half - chalked up Brisbane's eighth of the afternoon.
