Background Hypervirulent klebsiella pneumoniae (hvKP) is responsible for various invasive diseases and is associated with high mortality. However, the clinical and microbiological factors of hvKP infection to affect prognosis are not well studied. The purpose of this study is to evaluate prognostic factors of in-hospital mortality of hvKP infection, mainly focusing on clinical and microbiological characteristics. Methods A retrospective study was conducted in southwestern China from February 2018 to June 2019 and strains positive for aerobactin and string test were defined as hvKP. According to the clinical outcomes during hospitalization, hvKP infected patients were divided into non-survivor group and survivor group. The clinical characteristics, capsule serotypes, multi-locus sequence types, virulence genes and antimicrobial susceptibility were compared between the two groups. Results A total of 135 patients were classified as hvKP infection, with a prevalence rate of 22% and an in-hospital mortality rate of 11.9%. Univariate analysis exhibited that admission to intensive care unit (ICU)(p=0.008) and antimicrobial resistance of hvKP such as ampicillin/sulbactam(p=0.028), cefepime(p=0.033), aztreonam(p=0.049) and harboring iroN gene(p=0.023) were associated with higher in-hospital mortality. On the contrary, the rmpA gene showed an inverse association with in-hospital mortality(p=0.017). Multivariate logistic regression analysis revealed that admission to ICU (odds ratio [OR]=3.452, 95% confidence interval [CI]=1.052-11.329; P=0.041) and presence of iroN (OR=9.278, 95% CI=1.654-52.035; P=0.011) was considered to be the independent prognostic factors for in-hospital mortality of hvKP infection. Conclusion Emerging hvKP infection may lead to relatively high in-hospital mortality. Therefore, early surveillance and better management are necessary for patients admitted to ICU and infected with hvKP harboring iroN gene.