In conclusion, carrimycin and monomeric isovalerylspiramycin I inhibited the viability, colony formation, DNA replication, migration, invasion, and promoted apoptosis of HCC cells, and inhibited VEGF and PD-L1 protein expression, tumor growth, tumor histopathological alterations, and the concentration of VEGF in mouse serum. Here, CD274 is linked to hepatocellular carcinoma.