Objective To investigate the expressions of sulfiredoxin (Srx) and β-catenin in human cervical squamous cell carcinoma (CSCC) and their clinical significance. Methods Immunohistochemistry was used to detect the expressions of Srx and β-catenin in human cervical specimens, including normal cervical squamous cell epithelium tissues (NC), cervical intraepithelial neoplasia tissues (CIN), and CSCC. The correlation between Srx expression and β-catenin expression and the relationship of the two proteins to clinical the pathological features of cervical cancer were analyzed. Results The expression of Srx in CIN and CSCC was significantly higher than that in NC. In addition, Srx and β-catenin expressions were positively correlated to CSCC tissues. Furthermore, the up-regulated expression of Srx was significantly associated with lymph node metastasis, infiltration of vessels, and the depth of cancer invasion. However, its expression was not associated with age, tumor size, degree of differentiation, and International Federation of Gynecology and Obstetrics (FIGO) grade. Finally, the overexpression of β-catenin was significantly correlated with lymph node metastasis, degree of differentiation, and FIGO grade. However, β-catenin expression was not correlated with age, tumor size, and the depth of cancer invasion. Conclusion Srx and β-catenin are highly expressed in CSCC and associated with malignancy.