In summary, this study reveals that increased GUSB inhibits the expression of PD-L1 by promoting miR-513a-5p, leading to primary resistance to anti-PD1 treatment in HCC, and the use of amoxapine enhances the sensitivity of anti-PD1 treatment by inhibiting GUSB in HCC (Figure 9). Here, GUSB is linked to hepatocellular carcinoma.