OBJECTIVE Till now, cancer is a major health problem and one of the main causes of mortality worldwide. Ascorbic acid and selenium are the two most popular dietary supplements used to prevent cancer proliferative, therefore, the work aims to study the antitumor effect of ascorbic acid and selenium on HCT116 and MCF7 cell lines. METHODS In the present study, the cytotoxic effect of different concentrations of ascorbic acid and selenium on human breast cancer cell line (MCF7 cells) and human colon carcinoma (HCT116) was studied. RESULTS Viability % of HCT116 cell line and MCF7 cell line decreased with increasing ascorbic acid concentrations (1-4 mM). The 50% inhibitory concentration (IC50) of five dilutions of each concentration of ascorbic acid was evaluated in the current study. IC50 was 0.18, 0.17, 0.16, and 0.16 mM for HCT116 cell line and was 0.86, 1.34, 1.74, and 0.47 mM for MCF7 cell line at 1, 2, 3, and 4 mM, respectively. Cell viability decreased depending on the selenium concentrations ranging from 20 to 100 mM. Selenium effect showed less cytotoxicity on MCF7 compared to HCT116 cells at all tested concentrations where the cell viability at 20, 40, 60, 80, and 100 mM selenium was 33.74, 29.48, 26.08, 54.53, and 20.89 for HCT116 cell and was 79.53, 76.01, 59.42, 54.53, and 51.98 for MCF7 cell, respectively. Ascorbic acid induced apoptosis by promoting the release of lactate dehydrogenase (LDH) in HCT116 and MCF7 cells, but reduced release of LDH was observed in selenium treatment but increased when it added to ascorbic acid because of a possible synergistic action that may produce an enhanced anticarcinogenic effect. CONCLUSIONS The present study documented that a combination of ascorbic acid and selenium produces an additive chemopreventive effect on carcinogenesis.