Citrus fruits have been known to reduce the proliferation of many cancer cells. The antiproliferative effects of Citrus reticulata Blanco (CR) extract, the immature tangerine peel, on human gastric cancer cell line SNU-668 were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 4,6-diamidineo-2-phenylindole staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, reverse transcription-polymerase chain reaction expressions of BCL-2, BAX and CASP-3 genes, caspase-3 activity, and immunocytochemistry of caspase-3. From the results of the morphological and biochemical assays, CR (50 microg/ml) increased the apoptosis of human gastric cancer cells with typical apoptotic characteristics, including morphological changes of chromatin condensation and apoptotic body formation. CR (50 microg/ml) reduced the expression of BCL-2, whereas the expression of BAX and CASP-3 was increased compared with the control group. Furthermore, caspase-3 activity and caspase-3 protein expression in the CR-treated group was significantly increased compared with that in control group. These results suggest that CR may induce the apoptosis through the caspase-3 pathway in human gastric cancer cells.