BackgroundEvidence shows that genetic factors play important roles in the severity of coronavirus disease 2019 (COVID-19). Sulfatase modifying factor 1 (SUMF1) gene is involved in alveolar damage and systemic inflammatory response. Therefore, we speculate that it may play a key role in COVID-19.ResultsWe found that rs794185 was significantly associated with COVID-19 severity in Chinese population, under the additive model after adjusting for gender and age (for C allele = 0.62, 95% CI = 0.44–0.88,P= 0.0073, logistic regression). And this association was consistent with this in European population Genetics Of Mortality In Critical Care (GenOMICC: OR for C allele = 0.94, 95% CI = 0.90–0.98,P= 0.0037). Additionally, we also revealed a remarkable association between rs794185 and the prothrombin activity (PTA) in subjects (P= 0.015, Generalized Linear Model).ConclusionsIn conclusion, our study for the first time identified that rs794185 inSUMF1gene was associated with the severity of COVID-19.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12863-023-01133-6.