Osteopontin can stimulate macrophages to secrete colony stimulating factor (CSF1) through PI3K-Akt-p65 pathway, and then promote macrophage polarization by CSF1/CSF 1R pathway, up-regulate the expression of PD-L1 in HCC, create an inhibitory immune microenvironment, and induce immune escape of HCC. This evidence concerns the gene SPP1 and hepatocellular carcinoma.