Objective To explore the effects of morphine on growth of human esophageal cancer cell Ec109 and elucidate its possible molecular mechanism. Methods Ec109 cells were randomly divided into four groups: three groups of cells were treated with different concentrations of morphine (0.1,10 and 1 000 umol/L),and a control group was treated with normovolemic RPMI-l640 nutrient solution. Cells were incubated for 24,48 and 72 h,and rates of proliferation inhibition were determined by CCK-8 assay. Flow cytometry was performed after 48-h incubation to assess apoptosis and cell cycle distribution in the four groups. We also quantified the levels of p53 and caspase-3 mRNA using real-time PCR. Results Rates of proliferation inhibition were significantly higher in the three morphine-treated groups than in the control group(P<0.01);they were higher with higher morphine concentration and longer incubation(P<0.05). Proportions of apoptotic cells and cells in G1 phase were also higher in the morphine-treated cells at 48 h(P<0.05),and these proportions were higher with increasing morphine concentration(P<0.05). Levels of p53 and caspase-3 mRNAs were also up-regulated by morphine in a concentration-dependent manner(P<0.05). Conclusion These results suggest that morphine can inhibit proliferation of Ec109 cells by inducing apoptosis. Morphine may exert these effects,in part,by up-regulating p53 and caspase-3 expression.