Niya Mitchell scored 18 points while Richelle Velez chipped in 18 points off the bench while going 6-of-8 from three point range.
TSU led 32-15 at intermission fueled in large part behind the play of Mitchell and Velez.
Texas Southern shot 54 percent from the field while holding Huston-Tillotson to 27 percent for the game.
The Lady Tigers will close out non-conference play on the road at Texas Tech on Saturday.
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