Chemotherapy is the main treatment for advanced gastric cancer. However, the emergence of multidrug resistance (MDR) has become a major obstacle in chemotherapy in many tumors, including gastric cancer. Epithelial-mesenchymal transition (EMT), which is considered an important process in cancer development, also contributes toward tumor MDR. Salinomycin, an EMT blocker, shows broad-spectrum antitumor and chemosensitization properties. Here, we hypothesized that salinomycin could reverse the MDR of SGC7901/cisplatin (CDDP) gastric cancer cell by inhibiting EMT and further explored its possible underlying mechanisms. Our results indicated higher 50% inhibiting concentration (IC50) and stronger migration capacity in SGC7901/CDDP than in SGC7901 cells, whereas salinomycin could reduce the IC50 (50% inhibition of the concentration of chemodrugs after 4?μmol/l salinomycin treatment) and migration capacity in SGC7901/CDDP cells. At the molecular level, we found that the expression of E-cadherin, ZO-1 decreased, whereas the expression of N-cadherin, Vimentin, ZEB-1, and Twist increased in SGC7901/CDDP cells, and that salinomycin potently blocked the EMT by enhancing the expression of E-cadherin, ZO-1 and reducing the expression of N-cadherin, Vimentin, ZEB-1, and Twist in the above MDR cells. In addition, we also found that long noncoding RNA HOTTIP, an oncogenic regulator, was upregulated in SGC7901/CDDP cells, whereas its downregulation could markedly attenuate the EMT, thereby reversing the MDR. Furthermore, our data showed that the salinomycin-elicited MDR-reversion effect was associated closely with suppression of EMT through inhibition of the expression of long noncoding RNA HOTTIP. Collectively, our findings suggest a new underlying mechanism and applicable therapeutic regimen for MDR gastric cancer.