Efficient tumor-targeted co-delivery of PD-L1 siRNA and IL-2 Pdna achieves tumor-specific expression of IL-2 and down-regulation of PD-L1, increases infiltration and activation of CD8+ T cells in HCC, and induces a strong tumor-suppressive effect in HCC in synergy with a vaccine. This evidence concerns the gene CD8A and hepatocellular carcinoma.