Objective: To investigate the effect of nicotine on growth and apoptosis-related gene expression of human small lung cancer cell. Methods: NCI-H446 cell line was cultured in the presence of various concentrations (1(1000 ng/ml) of nicotine for 48 h. MTT was applied to evaluate the effect of nicotine on the growth of NCL-H446, small cell lung carcinoma (SCLC) cell line. After NCI-H446 cells were treated with 100 ng/ml for 48 h, human apoptosis-related gene cDNA expression profile microarray was used to detect the expression of 451 apoptosis-related genes in NCL-H446 cell line. Results: Significant proliferation promotion of nicotine (1(10 ng/ml) on NCI-LH446 cells were observed, but with decreased promotion effect with increased concentration of nicotine in culture. Growth inhibition rates for 1, 10, 100 and 1000 ng/m1 nicotine were -91.0%, -41.8%, -40.0% and 27.3% respectively. Microarray detection showed that significantly different expressions were found in71 of 451 apoptosis-related genes. 38 apoptosis-promoting gene and 30 apoptosis-inhibiting genes were up-regulated significantly (cy3/cy5>2.0), and only 3 showed significant down-regulation (cy3/cy5