Stress granules (SGs) are stalled translation initiation complexes comprising untranslated mRNAs and RNA-binding proteins (RBPs). RBP fox-1 homolog 2 (Rbfox2), a component of SGs, binds to retinoblastoma 1 (RB1) mRNA, which is closely related to cancer progression; however, the role of Rbfox2 in cancer progression remains largely unknown. In this study, we confirmed that Rbfox2, which is present in the nucleus as a splicing regulator, localizes to the cytoplasm of human colon cancer tissues and that induction of Rbfox2 dissociation from SGs by resveratrol treatment inhibits cancer progression. We also observed that Rbfox2 in SGs inhibited RB1 protein expression and promoted cell cycle progression. Additionally, resveratrol treatment inhibited SG-mediated Rbfox2 localization, further inhibiting RB1 protein expression, and inhibited specific Rbfox2 localization to the cytoplasm in melanoma B16-F10 cells, thereby effectively inhibiting metastasis and tumor growth ability. These results indicate that Rbfox2 dissociation from SGs attenuates cancer progression and offer insight into the mechanism associated with Rbfox2 dissociation, thereby marking Rbfox2 as a potential candidate target for cancer therapy.