Considering that the therapeutics targeting PD-L1 and Tregs either alone or in combination show great promise in the treatment of many cancers including HCC [75,76,77,78,79,80], the results of this study may therefore not only suggest the levels of PD-L1 expression and Tregs infiltration in tumor tissues as valuable prognostic biomarkers but also support PD-L1- and Tregs-targeted therapies as potential therapeutic options for pre-S2 mutant-positive HCC patients after curative surgical resection although the efficacy remains to be validated. The gene discussed is CD274; the disease is cancer.