Background: Resveratrol (RezV) which is found in several plants including grapes and types of berries has a vital role in inducing apoptosis and suppressing cell proliferation. Although the role of Bcl-2 in the apoptosis has been known in several pathways, the role and mechanism of miR-21 in the regulation of apoptosis in colorectal cancer (CRC) cells are unclear. Objectives: The main aim of this study was to evaluate the effects of RezV on the expression level of miR-21, Bax, and Bcl2 in colorectal tumor cells. Methods: In this study, the effect of RezV on the viability of CRC cells was evaluated by MTT assay. Then, the expression level of miR-21 was evaluated by real-time polymerase chain reaction (PCR) method. For evaluating HCT-116 cells apoptosis, the expression level of Bax and Bcl2 that are involved in the apoptosis pathway was investigated by the same method. Results: RezV inhibits the viability of HCT-116 cells. MiR-21 gene expression was decreased after 24 hours of treatment with RezV. The reduction of miR-21 expression leads to the reduction of the Bcl2 gene expression level. Moreover, increasing the Bax/Bcl2 ratio enhances HCT-116 cells apoptosis. Conclusion: In summary, RezV might be used as a co-treatment agent for CRC. On the other hand, conducting the in vivo study to evaluate the effects of RezV was critical.