Hawaii (11-4) pulled away during the middle of the second half with a 17-2 run to take its largest lead at 58-34.
Southern (3-11) had runs of seven and eight straight in the final 10 minutes but got no closer than 69-56 on Tre Lynch's jumper with 1:28 left.
Lynch led the Jaguars with 13 points and made all three of Southern's 3-pointers. Trelun Banks added 12 points.
Hawaii held Southern to 23 first-half points and Mike Thomas finished with five blocks.