〔Abstract〕 Objective To evaluate the expression of programmed death receptor ligand-1(SPP1), programmed cell death(PD-L1) in hepatocellular carcinoma(HCC), their correlation with M2-polarized macrophages, and their impact on prognosis. Methods Immunohistochemistry(IHC) was used to detect the expression of SPP1, PD-L1, and CD163(commonly used markers of M2-polarized macrophages) in 81 HCC patients. The correlation between the expression of SPP1, PD-L1, and CD163 and the clinical characteristics of patients and their prognosis were analyzed. The relationship between SPP1,PD-L1,and M2-polarized macrophages in HCC tissue was also analyzed. Results The expression of SSP1,PD-L1 and CD163 increased in HCC tissues compared with para-carcinoma tissues. The expression of SSP1,PD-L1 and CD163 were all related to the BCLC staging( P<0. 05),but were not related to age and sex. The expression of SSP1 was elevated in HCC patients with large tumor diameter and multiple intrahepatic tumors,PD-L1 was elevated in HCC patients with multiple intrahepatic tumors and HBV infection. SSP1,PD-L1 and CD163 were related to the prognosis,and high expression patients had lower 3-year OSR and OST compared to low expression patients. Cox analysis showed the BCLC staging,SPP1 and PD-L1 were independent prognostic factors. The expression of SPP1 and PD-L1 were positively correlated with M2 macrophages in HCC. Conclusion SPP1,PD-L1 and CD163 can be used to evaluate the biological behaviors of HCC,and the positive expression of SPP1 and PD-L1 suggests that HCC patients may have a poor prognosis.