A novel MRS model was established based on the LASSO regression coefficients of the genes PON1, IL15RA, NEIL3, HILPDA, PFN2, HAVCR1, ANXA10, CDCA8, EPO, S100A9, TTK, KLRB1, SPP1, STC2, CYP26B1, GPC1, G6PD, and CBX2. In either dataset, MRS was identified as an independent risk factor for OS in HCC patients. The gene discussed is SPP1; the disease is hepatocellular carcinoma.