High blood levels of beta-carotene and increased intake in the diets are inversely proportional to incidence of many cancer types. Antioxidant activity of beta-carotene was proposed to be related with its antitumor effect. Despite this plant derivative substance being sought in many cancer types, the effectiveness of beta-carotene against malignant mesothelioma remained unclear. Therefore, the present study aims to explore the impact of beta-carotene on cell viability, apoptosis, and oxidative stress in mesothelioma cells. Human mesothelioma cell SPC212 were treated with beta-carotene (3.125-200 mu M) for 24, 48, 72, and 96 h. Cytotoxicity was measured with the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide). Annexin-V/propidium iodide (PI) and caspase 3/7 biomarkers were used to identify apoptotic cells. Finally, the oxidative stress was evaluated with flow cytometry. The results of the measurements indicated a significant decline in viable mesothelioma cancer cell numbers upon p-carotene treatment in time- and concentration-dependent manner when compared to control cells. Furthermore, beta-carotene treatment led to apoptosis induction according to both annexin V/PI and caspase 3/7 assays. Furthermore, beta-carotene increased oxidative stress in SPC212 cells. These results show how beta-carotene affects proliferative, apoptotic, and oxidative properties in SPC212 malignant pleural mesothelioma cells and provide useful insights into future studies.