The relationship between smoking and esophageal squamous cell carcinoma (ESCC) has been confirmed by epidemiology. Cyclin D(1) plays a critical role in regulating the cell cycle; it is an important regulator of cell cycle and can function as a transcriptional co-regulator. The importance of cyclin D(1) makes it an attractive target for anticancer therapy. Human ESCC cell line EC109 was cultured with aspirin and cigarette smoke extract (CSE) at different concentrations for 48 h. Cell growth was tested with 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide reduction assay; cyclin D(1) mRNA level was detected by reverse transcription-polymerase chain reaction assays; protein level of cyclin D(1) was detected by Western blot; the cell cycle change was monitored by flow cytometry detection assays. CSE stimulated cell proliferation, increased the protein level of cyclin D(1) in a dose-dependent manner (P < 0.01), and decreased the proportion of G(0)/G(1) phase cell of cell cycle. However, aspirin can inhibit the cell growth and suppress the protein level of cyclin D(1) after CSE affected the EC109 cell line in a dose-dependent manner (P < 0.01). Meanwhile, aspirin increased the proportion of G(0)/G(1) phase cell, while that of S and G(2)/M phases decreased. Aspirin can inhibit the cell growth and suppress the protein level of cyclin D(1) after CSE affected EC109 cell line. The probable mechanism is through decreasing the expression of cyclin D(1), thus stopping the transition of cell cycle from G(0)/G(1) to S phase.