Rashard McGill and Jonathan Mills added 10 points apiece as the Golden Eagles (27-9), who will advance to take on the BYU Cougars in the next round. Mills and McGill also accounted for eight rebounds each in the win.
Southern Miss managed to hit only 1-of-15 from 3-point range, but Neil Watson led a tough defense with four steals as USM moved on to the NIT's third round, where they will host No. 3 Brigham Young.
Louisiana Tech (27-7) was led by Raheem Appleby with 17 points.
Alex Hamilton contributed 15 and six assists for the Bulldogs.