Abstract: Objective The objective of this study was to construct phylogenetic trees based on HPV53 full length sequences, as well as to predict the physical and chemical parameters, secondary structure, B and T cell epitopes of HPV53 proteins (E1, E2, E4, E6, E7, L1, and L2). Method Full length of HPV53 variants were Obtained from the GenBank and a phylogenetic tree was constructed to define variant lineages. The physical and chemical parameters of HPV53 proteins were analyzed by ProtParam. The secondary structure of proteins was analyzed using PSIPRED and SOPMA. The B and T cell epitopes for HPV53 proteins were predicted by the IEDB analysis server and the ABCpred server, respectively. Then, to select the potential dominant B and T cell epitopes, more parameters including flexibility, hydrophilicity, surface accessibility, antigenicity of predicted B and T cell epitopes were further predicted by bioinformatic methods (e.g., DNASTAR-Protean, VaxiJen, etc.). Finally, for homology analysis, the potential dominant B and T cell epitopes were compared with the 13 high-risk HPV subtypes using NCBI BLAST tool. Results Phylogenetic analyses clustered HPV53 variants into 3 lineages designated A, B, and C. The physicochemical properties of three different HPV53 variants (representing A, B, and C lineages, respectively) were similar, while slight differences in secondary structure were observed. There were 6 potential dominant B cell epitopes and 9 potential dominant T cell epitopes were predicted for HPV53 proteins. Among these epitopes, B cell epitopes TTPIRPPPPPRPWAPT in E4 region and CYRCQHPLTPEEKQLH in E6 region, and T cell epitopes SGVHSYEEIPMQ in L2 region showed high homologous to HPV56 (all＞90%). Conclusions Using bioinformatic tools, B and T cell epitopes for all proteins of HPV53 were predicted, which provides the basis for further research on epitope vaccines against HPV53.