Objective:To investigate the serum level of soluble PD-1 (sPD-1) in hepatocellular carcinoma (HCC) patients and its relationship with the clinical prognosis.Methods:21 patients with HCC underwent radical resection in Chifeng Municipal Hospital from November 2019 to June 2020 were enrolled. Among them, 15 patients were male and 6 female, aged from 40 to 81 years, with a median age of 58 years. Serum sPD-1 level was detected by ELISA, and the expression level of PD-1 in cancer tissues was determined by immunohistochemical staining. The relationship among serum sPD-1 level, PD-1 expression level in cancer tissues and clinicopathological parameters of HCC patients was assessed by Spearman rank correlation analysis. Literature search related to the relationship among serum sPD-1 level, PD-1 expression level in cancer tissues and clinical prognosis of HCC was conducted in CNKI, Wanfang Data, Chinese Biomedical Database (CBM), PubMed, Cochrane Library and Embase, and a Meta-analysis was carried out.Results:The median serum level of sPD-1 in HCC patients was 1 365 (589-3 315) ng/L. The positive rate of PD-1 in cancer tissues was 95% (20/21), including 11 cases of weakly positive expression and 9 cases of moderately positive expression. Spearman analysis showed that preoperative serum sPD-1 level was negatively correlated with the expression intensity of PD-1 in cancer tissues (rs=-0.566, P<0.05). The positive expression intensity of PD-1 in cancer tissues was negatively correlated with the pathological differentiation (rs=-0.513, P<0.05), whereas the serum level of sPD-1 was positively correlated with pathological differentiation (rs=0.536, P<0.05). Significant difference was observed in the overall survival between high and low PD-1 expression groups by Meta-analysis (HR=1.30, 95%CI: 1.02-1.65, P<0.05). The serum level of sPD-1 was not correlated with the overall survival (HR=0.95, 95%CI: 0.32-2.97, P>0.05).Conclusions:The serum level ofsPD-1 in HCC patients is negatively correlated with the expression intensity of PD-1 in cancer tissues, and both of them are associated with the pathological differentiation. HCC patients with high expression of PD-1 in cancer tissues have poorer prognosis.