〔Abstract〕 Objective To explore the nucleotide variation and protein amino acid changes of E4 and L2 genes ofHuman Papillomavirus16(HPV16), and to analyze the evolutionary characteristics of HPV16 virus. Methods 40 HPV16 infection-positive cervical exfoliated cells samples and tissue cell samples were collected from hospital, viral DNA was extracted, Sanger sequencing perform in cervical exfoliated cells DNA and high-throughput sequencing technology sequenced in cervical tissues DNA for E4 and L2 genes of HPV16, HPV16 E4 and L2 gene phylogenetic evolution trees were constructed, and variation of HPV16 E4 and L2 genes were analyzed. Results There were 72 HPV16 E4 variant samples with nucleotide variants(4 missense mutations and 7 synonymous mutations) at 10 sites, HPV16 L2 gene variants in 74 samples, and nucleotide variants(23 missense mutations and 18 synonymous mutations) at 40 sites. The variation frequency of T4177C, A4288C and A4654C in cervical cancer was significantly higher than that in non-cervical cancer, and the difference was statistically significant(P<0.05). Conclusion (1) The main HPV16 virus strains in Xinjiang are European strains, and a few are Asian strains.(2) The mutation frequency of T4177C, A4288C and A4654C in HPV16 L2 gene is higher than that in non-cervical cancer, and G4181A is related to the Asian strain.