To determine whether pretreatment CYFRA 21-1 levels can be a useful prognostic indicator in cervical cancer with reference to squamous cell carcinoma-antigen (SCC-Ag). We retrospectively analyzed data on 506 consecutive cervical cancer patients who were treated by radical hysterectomy or primary concurrent chemoradiation therapy. The pretreatment serum SCC-Ag and serum CYFRA 21-1 levels were measured in these patients. A multivariate analysis using Cox’s proportional hazard model was performed to evaluate the prognostic significance of pretreatment variables. In patients who underwent radical hysterectomy, there was a significant correlation between pretreatment serum SCC-Ag/CYFRA 21-1 levels and patient age, advanced International Federation of Gynecology and Obstetrics (FIGO) stage, large tumor size, lymph node metastasis, and deep stromal invasion. In the stepwise Cox regression analysis, large tumor size > 4cm was an independent prognostic factor for disease-free survival (OR, 3.110; [95% CI, 1.588-6.093], P=0.001) and overall survival (OR, 8.497; [95% CI, 1.797-40.184], P=0.007) in patients with squamous cell carcinoma, while pretreatment CYFRA 21-1(P=0.010) serum levels had a significant independent effect on overall survival. Likewise, pretreatment CYFRA 21-1(p<0.001 and P=0.006) serum levels were the only independent prognostic factor for disease-free survival and overall survival in patients with non-squamous cell carcinoma. Pretreatment CYFRA 21-1 levels may be considered as a useful prognostic indicator in cervical cancer with reference to SCC-Ag.