Our study aimed to investigate the association of Pyruvate Kinase isozyme type M2 (PKM2) with radiation resistance in locally advanced cervical squamous cell carcinoma (LACSCC). We retrospectively reviewed 132 female patients who received primary radiation therapy to treat LACSCC at Federation Internationale of Gynecologie and Obstetrigue (FIGO) stages IB-IVA. Forty-seven patients with progression free survival (PFS) of less than 36 months were regarded to have radiation resistance. Eighty-five patients with PFS no less than 36 months were regarded as radiation sensitive. Using immunohistochemistry, we found that the overexpression rate of PKM2 in radiation resistant and radiation sensitive patients was 87.2% and 57.6%, respectively, and the difference was statistically significant (p<0.001). The 5-year progress free survival rates in patients with low and high expression of PKM2 was 80.4% and 60.5%, respectively, and the difference was statistically significant (p=0.008). Multivariate Cox regression analysis identified that high expression of PKM2 is an independent negative prognostic factor in cervical cancer patients [Hazard ratio (95% CI), 2.888 (1.347, 6.194) p=0.006]. These results demonstrate that overexpression of PKM2 contributes to radiation resistance and acts a poor prognosis indicator in patients with LACSCC.