[3] Hufanga committed to the University of Southern California (USC) to play college football.

[4][5][6] As a true freshman at USC in 2018, Hufanga played in eight games with five starts before suffering a season-ending broken collarbone.

[9][10] He and BYU quarterback Zach Wilson were selected as co-recipients of the 2020 Polynesian College Football Player of the Year Award.

[18] In the Divisional Round of the playoffs against the Green Bay Packers, he recovered and returned a blocked punt for a critical touchdown which eventually set up a 13–10 victory for the 49ers.

[25] In Week 11 of the 2023 season, Hufanga suffered a torn ACL and was placed on injured reserve on November 21, 2023.

[27] Without Hufanga, the 49ers reached Super Bowl LVIII but lost 25–22 to the Kansas City Chiefs.