Abstract： Objective To investigate the expression and significance of HPV 16/18,31/33 DNA and Rb-related Tumor Gene Proteins p16ink4a CyclinD1,CDK4,Rb,E2F-1,Ki-67 in invasive squamous cell carcinoma of cervix(ISSC).To study the correlation of their expression and clinical pathological parameters of ISCC.Methods HPV16/18,31/33 DNA were detected by situ hybridization in 73 ISCC cases,30 cases of high-grade squamous intraepithelial lesions(HSIL),32 cases of low grade squamous intraepithelial lesion (LSIL),and 21 cases of normal cervical squamous epithelium(NCE);Two-step immunohistochemical method wag used to detect the expression of p16ink4a,CyclinD1,CDK4,Rb,E2F-1 and Ki-67 protein in ISCC,HSIL,LSIL and NCE. Results Overall expression of HPV 16/18. 31/33 in the four groups was statistically significant difference(P<0.01);intravenous tumor thrombus more likely occured in HPV 16/18 infection cases than non-infection(OR=3.875);HPV3 1/33 infection cases with high rate of clinical stage progress(OR=3.5).Overall expression of p16ink4a CyclinD1,CDK4,Rb,E2F-1 and Ki-67 in the four groups was statistically significant difference(P<0.01).Rb and Ki-67 were positively correlated(rs=0.250);p16ink4a and the malignancy degree of tumor cells were negatively correlated(OR=0.942);CDK4 and the malignancy degree of tumor cells were positively correlated(OR=1.033);The age and the clinical stage were positively correlated(OR=1.063). Conclusion HPV16/18. 31,33 infection is closely related to the occurrence and development of cervical squamous cell carcinoma;CDK4,Ki-67 can be used 8.8 an objective marker in diagnosis of cervical lesions;The mechanisms of Rb protein in ISCC need be further investigated.