In our study, we observed the miR-302b’s function of suppressing proliferation in human hepatoma cell lines and found that ectopic overexpression of miR-302b could enhance the sensitivity of HCC to 5-FU by negatively regulating DPYD and anti-apoptosis protein Mcl-1, which suggests that miR-302b might serve as a therapeutic reagent for HCC. The gene discussed is DPYD; the disease is hepatocellular carcinoma.