In this report, we demonstrate that Gemcitabine upregulates NKG2D ligand expression on tumor cells via the activation of ataxia-telangiectasia-mutated (ATM) and ATM-and Rad-3-related protein kinases (ATR) pathway resulting in an enhanced NK cell-mediated cytotoxicity, while Gefitinib downregulates NKG2D ligands expression via inhibition of the EGFR/PI3K signalling thereby hindering NK cell killing. Here, ATR is linked to neoplasm.