[Background] HPS is the pathogen of Gl?sser’s disease. Due to the drug resistance caused by long-term use of antibiotics and the lack of interactive immune protection of inactivated vaccines, it’s impossible to effectively prevent and control Gl?sser’s disease at present. [Objective] The purpose of this study was to understand the serotypes, genotypes and drug resistance characteristics of HPS in Anhui province, and to prevent and control Gl?sser’s disease more effectively. [Methods] The serotypes of 44 strains of HPS, isolated in Anhui province from 2008 to 2017 were identified by polymerase chain reaction (PCR), the genotyping was carried out by MLST, and MIC was determined by microdilution method. [Results] A total of 6 serotypes (1, 4, 5, 7, 13 and 14) were detected in 44 strains of HPS, serotypes 4 and 13 were dominant serotypes, each accounting for 40.91%. A total of 9 ST types (ST241, ST267, ST268, ST269, ST270, ST271, ST272, ST273 and ST274) were detected in MLST classification, the dominant genotypes were ST267 and ST268, respectively accounting for 40.91%. Drug resistance analysis showed that the susceptibility rates of gentamycin (GEN) and penicillin (PEN) were 100% and 93.2%, respectively. There were 86.4% of the isolates showed multiple drug resistance, and there were 33 types of multi-drug resistance spectrum, among which the ratio of COT-TET was the largest (42.4%). [Conclusion] The epidemic serotypes and genotypes of HPS in Anhui province are diversified, with high genetic heterogeneity and severe multi-drug resistance. There was no significant correlation between serotype, ST type and drug resistance.