Abstract: Objective To investigate the expressions of ΔNp63α, DPC4/Smad4 and P21 in cervical squamous cell carcinomas and explore their implications in tumorigenesis, progression and prognosis of the malignancy. Methods The expressions of ΔNp63α, DPC4/Smad4 and P21 were examined with immunohistochemistry in 100 specimens of cervical squamous cell carcinoma, 40 specimens of cervical intraepithelial neoplasia (CIN) and 40 specimens of normal cervical tissues to explore their associations with the occurrence, progression and prognosis of cervical squamous cell carcinoma. Results The expressions of ΔNp63α and DPC4/Smad4 decreased and P21 expression increased significantly in the order of normal cervical tissue, CIN and cervical squamous cell carcinoma (P<0.01), and their expressions were associated with the differentiation, clinical stages and lymph node metastasis of cervical squamous cell carcinoma (P<0.01). The expression of ΔNp63α was positively correlated with the expression of DPC4/Smad4 (r=0.581, P<0.05), and they were both negatively correlated with P21 expression (r=-0.449 and -0.254, respectively; P<0.05). Kaplan-Meier survival analysis showed that patients with cervical squamous cell carcinoma positive for ΔNp63α and DPC4/Smad4 had a significantly higher 5-year survival rate than those negative for ΔNp63α and DPC4/Smad4 (P<0.001); the patients positive for P21 had a significantly lower 5-year survival rate than the P21-negative patients (P<0.005). Conclusions The expressions of ΔNp63α, DPC4/Smad4 and P21are related with the differentiation, invasion, lymph node metastasis, pTNM stage and prognosis of in cervical squamous cell carcinomas, suggesting their value as potential markers for prognostic evaluation of patients with cervical squamous cell carcinoma.