In this study, we demonstrated that a combination of HBV pre-S2 mutant and higher levels of PD-L1 expression and Tregs infiltration in tumor tissues was an independent prognostic biomarker with greater performance in identifying patients at a higher risk of HCC recurrence after curative surgical resection than that of either one or a combination of either two of these three biomarkers. Here, CD274 is linked to neoplasm.