The Wolfpack led 16-8 after the first quarter, 30-14 at halftime, and took a 41-22 lead into the final eight minutes.
Misty Bruhn netted three three-balls to lead Cherokee's scoring with nine points, and Shelby Dilla added six points. Shantell Grilton led HWC with 12 points, and Kayla Gresink tallied 11.
Jackie Wilson led Cherokee in rebounding with four, and Bruhn pocketed three. Lauren Husman, Kelsie Peterson, and Shanon Shaefer each tallied three steals for the host team.
"Shelby and Misty showed great senior leadership tonight," said Cherokee first-year coach Abby James. "The are both working hard on both ends of the court.
"Our posts really struggled tonight. Hull Western Christian kept the ball out of their hands and the posts struggled with doing their job on the boards. Our posts need to get more physical offensively and defensively.
"Senior (scoring leader) Kelsie Peterson injured her knee and freshman Shanon Shaefer did a nice job coming in from the bench ready to go. Our bench has done a great job this year stepping in."