Objective: To investigate the relationship between nuclear factor-kappaB (NF-κB), multiple tumor suppressor gene (P16) and clinical features of cervical cancer as well as sensitivity to radiotherapy. Methods: Retrospective collection of clinical data from 119 patients with cervical cancer. All patients were tested for the positive expression of NF-κB and P16 in cervical cancer cells. The relationship between their expression and clinical features as well as sensitivity to radiotherapy was analyzed. Results: Among the 119 specimens, 88 (73.95%) were positive for NF-κB and 97 (81.51%) were positive for P16. The positive expression rates of NF-κB and P16 showed significant differences between patients with varying degrees of differentiation and patients with/without lymph node metastasis (P<0.05). Spearman correlation analysis revealed that the positive expression rate of NF-κB was positively correlated with the degree of differentiation and lymph node metastasis (P<0.05), whereas the positive expression rate of P16 was negatively correlated with these clinical features (P<0.05). Univariate and multivariate Logistic regression analyses indicated that lymph node metastasis and NF-κB positivity were independent risk factors for insensitivity to radiotherapy, whereas P16 positivity was an independent protective factor against (P <0.05). Conclusion: NF-κB and P16 are closely related to the degree of differentiation and lymph node metastasis in cervical cancer. The positive expression of NF-κB and the positive expression of P16 are influencing factors for insensitivity to radiotherapy.