Objective To explore the expression of the paraoxonase-1(PON1)gene in hepatocellular carcinoma(HCC)and its clinical prognostic significance,as well as immune infiltration analysis.Methods Firstly,the gene ex-pression levels and prognostic value of PON1 in HCC patients were obtained from online databases,including TIMER,HCCDB,and Kaplan-Meier Plotter.Then,90 HCC patients who underwent surgical resection at the Affiliated Tumor Hospital of Guangxi Medical University from April 2011 to June 2015 were included,and the expression levels of the PON1 gene in both tumor and adjacent liver tissues were detected.Cox regression analysis was conducted to select pa-rameters with significant prognostic value and construct a prognostic model.Finally,correlation analysis was performed to evaluate immune cell infiltration characteristics.Results The gene level of PON1 was significantly lower in HCC than in adjacent tissues,and low expression of PON1 was associated with poor prognosis of HCC(P<0.05).PON1 mRNA levels,BCLC staging,CNLC staging,T stage,number of microvascular invasions,vascular invasion,and serum AFP were significantly correlated with HCC prognosis(P<0.05).BCLC staging,serum AFP,and PON1 mRNA levels were identified as independent risk factors for the prognosis of HCC patients.The prognostic nomogram based on these three indicators showed good predictive ability for the 1-,2-,and 3-year overall survival rates of HCC patients(C-index=0.757).Im-mune infiltration analysis revealed significant correlations between PON1 and various immune infiltrating cells in HCC(P<0.05).Conclusion Low expression of PON1 can serve as a potential biomarker for poor prognosis in HCC patients.A predic-tive model combining PON1,serum AFP,and BCLC staging can provide individualized prognostic prediction for HCC patients.