Oral squamous cell carcinoma (OSCC) is one of the most common carcinomas in the head and neck area. Bitter melon extraction (Momordicacharantia, BME) has been used as a functional food to prevent and treat human health related issues. It has recently been reported that BME inhibits breast cancer cell growth by arresting cell cycle and promoting apoptosis. In this study, we aimed at proving the inhibitory action of BME on OSCC proliferation. We used two OSCC cell lines, SCC4 and Ca9-22. Both cell lines were treated with different concentrations (1%, 2%, and 5%) of BME. Cell viability was examined by MTT assay. DNA condensation was visualized by immunofluorescence microscope to determine the signs of the cell apoptosis. Cell numbers were significantly decreased in a dose-dependent manner by bitter melon at concentration of 1% of BME on Ca9-22 cell line (P=0.001) but no significant effect on SCC4 (P=0.124) at the same concentration. 2% BME treatment of the Ca9-22 cell line induces chromatin condensation and DNA fragmentation after 20 hours. It seems that BME inhibits the proliferation of Ca9-22 cell line by inducing apoptosis. Thus, BME may be used as a dietary supplement for prevention of OSCC.