In this study, we showed that prior TKI treatment renders HCC insensitive to subsequent immunotherapy, at least in part, through the impairment of TNF-α and STING-IFN-α signaling and immunogenic cell death, which may lead to reduced intratumoral infiltration of CD8+ T cells and cDC1 dendritic cells. Here, STING1 is linked to hepatocellular carcinoma.