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Cancer-associated fibroblasts (CAFs) are a major component of hepatocellular carcinoma (HCC) stroma that are critically involved in HCC cancer chemoresistance, but the mechanism has not been elucidated. Previous studies have reported CD73 exerted an immunosuppressive function in cancer. Here, we explored the mechanism by which CAFs regulates CD73 HCC cells and clarified whether CAFs promote chemoresistance of CD73 cells. We used the co-culture method to study the relationship between CAFs and HCC cells. Immunohistochemistry was applied