Based on the other S100 family members (S100A1, S100A2, S100A3, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, S100A12, S100A13, S100A14, S100A16, S100B, and S100P), we utilized LASSO regression analysis to develop a prognostic model for patients with HCC and finally built an 8-mRNA-based signature (S100A1, S100A4, S100A9, S100A10, S100A11, S100A12, S100A14, and S100A16) for predicting OS. This evidence concerns the gene S100A9 and hepatocellular carcinoma.