Multiple drug resistance, a phenomenon in which cancer cells that acquire resistance to one type of anticancer drug are also resistant to several other drugs, often quite different in both structure and mechanism of action, has been studied. Our previous studies have identified a novel oxaliplatin resistance factor by analyzing heat shock protein 70 (Hsp70) interacting proteins. Hsp70, a stress response molecule, has been reported to be involved in the resistance to several anticancer drugs, including oxaliplatin. This study analyzed Hsp70-interacting proteins and then identified novel molecules that contribute to multidrug resistance. To identify Hsp70 interactors critical for oxaliplatin, 5-fluorouracil, paclitaxel, and irinotecan resistance in human gastric cancer cells, OCUM-2M, we performed mass spectrometry-based proteomic analysis using affinity purification with anti-Hsp70 antibodies. This led to the identification of six Hsp70 interactors common to the four resistant cell lines. These six candidates were then subjected to RNAi screening to assess drug sensitivity. Two candidates contributed to cell proliferation, while the other four candidates increased sensitivity to anticancer drugs. These results suggest that Hsp70 interactors cause multiple drug resistance.