We observed that upregulation of PDL1 was induced by overexpression of YBX1 or TAGLN2, and YBX1 were positively correlated with the percentage of PDL1+ in GC; therefore, elevated expression of the TAGLN2-YBX1-ISGs axis proteins might resensitize IFN-related DNA damage-resistant tumors to PD-1/PDL1-targeting immune checkpoint blockade (ICB) therapy. The gene discussed is YBX1; the disease is gastric cancer.