Abstract: OBJECTIVE To investigate the changes of high risk (HR) HPV DNA load, HPV16-E7 protein and VEGF_C expression and their predictive value in cervical squamous cell carcinoma after recombinant human interferon α₂β treatment. METHODS The 35 cases of chronic cervicitis, 25 cases of cervical precancerous lesions and 30 cases of cervical cancer were selected as study subjects. Patients were treated with recombinant human interferon α₂β. The expression levels of HPV16-E7 protein and VEGF_C were detected by SP immunohistochemistry before and after treatment while the second generation hybridization capture method was used to dectect HR HPV DNA load. The application of SPSS software analysis of HR HPV DNA load, HPV16-E7 protein and VEGF_C for cervical squamous cell carcinoma predictive value. RESULTS After treatment, the HPV-DNA load in cervical cancer group was significantly higher than that in precancerous lesions group (P<0.05), and it was significantly higher in precancerous lesions group than that in chronic cervicitis group (P<0.05). Compared with before treatment, the expression of HPV16-E7 protein and VEGF_C were not significantly decreased, but were significantly higher in cervical precancerous lesions than those in chronic cervicitis (P<0.05). Cervical squamous cell carcinoma was significantly higher than that in precancerous lesions (P<0.05). Multivariate stepwise logistic regression analysis showed that cervical cancer=-2.763+0.275 HR HPV DNA load+1.581 HPV16-E7 protein+1.216 VEGF_C (c²=36.781, P<0.001). The results of hosmer-leme-show showed that there was no significant different between observation data and forecast data. The ROC curve showed the highest AUC (0.91) for HR HPV DNA load, HPV16-E7 protein and VEGF_C combined for predicting cervical squamous cell carcinoma. CONCLUSION The effect of HR HPV DNA load combined with HPV16-E7 protein and VEGF_C on cervical squamous cell carcinoma is great after recombinant human interferon α₂β treatment.