Gastric cancer (GC) is one of the most common cancers worldwide and results in the second greatest rate of cancer-associated mortality globally. Multidrug resistance (MDR) often develops during the chemotherapy, resulting in the failure of treatment. To investigate the molecular mechanism of MDR, the roles of microRNA (miR)-1 were studied in GC. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to investigate the expression levels of miR-1 and sorcin in SGC7901/ADM and SGC7901/VCR cell lines. The effect of miR-1 on the half maximal inhibitory concentration (IC 50 ), cell apoptosis rates and drug accumulation was uncovered by MTT assay and flow cytometric analysis. Furthermore, dual-luciferase assay and western blotting were used to determine the target of miR-1 in GC. It was demonstrated that miR-1 was highly downregulated in MDR GC cell lines, including SGC7901/ADM and SGC7901/VCR. Overexpression of miR-1 in MDR GC cells decreased IC 50 , but increased the cell apoptosis rates and promoted the drug accumulation in cancer cells. Dual-luciferase activity assay indicated that sorcin was the target of miR-1 in GC. In addition, overexpression of sorcin could partially reverse the effect of miR-1 in MDR GC cells. The role of miR-1 in MDR GC cells makes it a potential therapeutic target for a successful clinical outcome.