Hyperoside (HYP) exhibits diverse pharmacological effects and holds potential for enhancing chemotherapy sensitivity. However, few studies have reported the impact of HYP on the malignant progression of esophageal carcinoma (EC) and its sensitivity to radiotherapy. The impact of HYP on the viability of esophageal carcinoma cells (TE-1 and KYSE-150) was assessed using Cell Counting Kit-8 (CCK-8) assays. The biological characteristics and radiosensitivity of esophageal carcinoma cells following HYP treatment were evaluated through clone formation experiments, flow cytometry, scratch wound-healing assays, and transwell migration and invasion assays. Western blot analysis was performed to determine the levels of proteins associated with cell death and epithelial-mesenchymal transition (EMT), as well as to explore whether HYP interferes with the radiosensitivity of esophageal carcinoma cells via the STAT3/AKT/ERK pathways. Finally, a subcutaneous graft tumor model was constructed to investigate the effects of HYP and X-ray treatments on in vivo tumor growth. The findings indicated a dose-dependent decrease in the survival rate of KYSE-150 and TE-1 cells following HYP treatment. HYP treatment also inhibited cell proliferation, invasion, migration, and EMT, while increasing the apoptotic rate and radiosensitivity of the cells. Notably, HYP suppressed the malignant progression of EC and enhanced radiosensitivity via the STAT3/AKT/ERK pathway. Moreover, HYP impaired the growth of esophageal carcinoma tumors in mice, with the combined HYP and X-ray treatment exerting a stronger inhibitory effect. In conclusion, HYP increases the radiosensitivity of esophageal carcinoma cells, offering considerable promise for application in the clinical treatment of EC.