Objective:To explore the mechanism of microRNA(miR) -191-5p in regulating cisplatin resistance in esophageal cancer cells by targeting phospholipase CD1(PLCD1). Methods:The expression of miR-191-5p in esophageal cancer cell line ECA109/DDP(cisplatin-resistant) was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) after respective transfection with mimic R-191-5p and negative control. The expression of miR-191-5p between drug-resistant cell line ECA109/DDP and parent cell ECA109 was compared. The transfected ECA109/DDP cells were treated with DDP. The sensitivity of transfected ECA109/DDP cells to cisplatin was detected by MTT assay. The expression of PLCD1 protein was detected by Western blotting. The interaction between miR-191-5p and PLCD1 was validated by Dual Luciferase Target Test. Results:The expression of miR-191-5p in drug-resistant cells ECA109/DDP was significantly lower than that in parent cells ECA109. The expression of miR-191-5p in ECA109/DDP cells transfected with mimic of miR-191-5p was significantly higher than that in control cells transfected with negative miR-191-5p. After DDP treatment, the proliferation activity of ECA109/DDP cells was decreased by the transfection of mimic R-191-5p. Western blotting showed that the expression of PLCD1 protein in the mimic group of miR-191-5p was significantly lower than that in the negative control group(P<0.05). Double luciferase target experiment proved that PLCD1 was the direct target of miR-191-5p. Conclusion:miR-191-5p may inhibit cell proliferation by targeting PLCD1, and then reverse the resistance of ECA109/DDP cells to DDP.