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AIM:To study the effect of nicotine on the migration and invasion of human esophageal squamous carcinoma cells and to investigate whether nimesulide can inhibit the effect of nicotine. METHODS:The esophageal squamous carcinoma cell line (TE-13) was treated with different concentrations of nicotine (100 mg/mL and 200 mg/mL) or 200 mg/mL nicotine plus 100 mmol/L nimesulide. Cell migration and invasion were measured using migration and invasion chamber systems. COX-2 expression was determined by West blotting. Matrix metalloproteinase-2 (MMP-2) was analyzed by zymography and ELISA. RESULTS:Nicotine (100 mg/mL, 200 mg/mL) enhanced TE-13 cells migration and invasion, and increased the protein expression of COX-2 and the activity of MMP-2. Nicotine (200 mg/mL) stimulated TE-13 cells migration and invasion which were partly blocked by nimesulide. This was associated with decreased protein expression of COX-2 and decreased activity and protein expression of MMP-2.CONCLUSION:Nicotine enhances the migration and invasion of the esophageal squamous carcinoma cell line, and nimesulide partly blocks the effect of nicotine-enhanced esophageal squamous carcinoma cell migration and invasion.