Although we have already identified several biomarkers to predict prognosis and evaluate the efficacy of treatment for HCC, such as alpha-fetoprotein (AFP) [25], Des-Carboxy Prothrombin (DCP) [26], osteopontin (OPN) [27], vascular endothelial growth factor (VEGF) [28], and Golgi protein 73 (Gp-73) [29, 30], representative and credible biomarkers that could precisely reflect the immune modulation of the TME are highly desirable. This evidence concerns the gene SPP1 and hepatocellular carcinoma.