Objective:To investigate the expression, prognostic value of acylphosphatase 1 (ACYP1) and its relationship with hepatocellular carcinoma (HCC) immune cell infiltration.Methods:The expression of ACYP1 in 374 cases of HCC was analyzed by using The Cancer Genome Atlas (TCGA) database. According to the median expression level of ACYP1 in HCC, the patients were divided into high expression (187 cases) and low expression group (187 cases). Fifty normal liver tissue were used as negative control. The differential expression, Kaplan-Meier survival analysis, univariate and multivariate Cox analysis were performed to evaluate the role of ACYP1 in the diagnosis and prognosis of HCC. The relationship between the expression level of ACYP1 and immune cell infiltration and immune checkpoint were analyzed through the TIMER database.Results:The expression level of ACYP1 in HCC (2.18±0.69) was higher than that in normal liver tissue (1.02±0.31), and the difference was statistically significant ( t=11.76, P<0.001). The survival of HCC patients with high ACYP1 was shorter than those HCC patients with low ACYP1 expression, and high expression of ACYP1 was an independent risk factor for poor prognosis of HCC patients ( HR=2.402, 95% CI: 1.483-3.891, P<0.05). The area under the curve of ACYP1 expression level in diagnosis of HCC was 0.965. The expression level of ACYP1 was significantly positively correlated with immune cell infiltration and immune checkpoints programmed cell death protein 1( r=0.288, P<0.001) and cytotoxic T lymphocyte-associated antigen 4 ( r=0.311, P<0.001). Conclusion:ACYP1 is a potential biomarker for HCC diagnosis and prognosis , as well as a potential therapeutic target.