Introduction: SOX2 is a key player in tumor development, the maintenance of cancer stem cells, and the progression of cancer. However, the regulatory mechanisms of SOX2 expression in human breast and prostate cancers are still not well understood. Methods: SOX2 expression in prostate and breast cancer tissues, as well as in corresponding cell lines, was analyzed using qRT-PCR, Western blotting, and immunohistochemistry. Functional assays including cell proliferation, migration, and apoptosis were performed following SOX2 knockdown and treatment with epigenetic modulators. Chromatin immunoprecipitation (ChIP) was also conducted to explore histone modifications. Results: SOX2 was significantly overexpressed in prostate and breast cancer tissues. Cancer cell lines such as DU145 and PC3 (prostate) and MCF7 and MDA-MB-231 (breast) also displayed elevated SOX2 levels. SOX2 inhibition led to a marked reduction in cell proliferation and migration. Treatment with epigenetic modulators further upregulated SOX2 expression in both cancer types. DNA methylation patterns in the SOX2 promoter region did not account for the overexpression. Instead, the activation of the SOX2 promoter was attributed to an increased presence of activating histone marks like H3K4me3 and H3K9acS10p, alongside a decrease in repressive marks H3K9me3 and H3K27me3. Conclusion: Histone modifications play a pivotal role in SOX2 overexpression, which contributes to tumor growth and cancer progression. These findings suggest that dual-targeting SOX2 and its associated epigenetic regulators may offer an effective therapeutic strategy for aggressive prostate and breast cancers.