The positive correlation of LY6E, IFITM1, GADD45A, and SPP1 with different immune checkpoints suggested that the expression levels of checkpoints related to the four characteristic genes could be predicted to some extent by detecting LY6E, IFITM1, GADD45A, and SPP1 in HCC, and thus the sensitivity of targeted therapy. Here, SPP1 is linked to hepatocellular carcinoma.