Objective To investigate the current situation and influencing factors of the core competence of infection control nurses in Henan Province, and provide reference for improving the core competence of infection control nurses. Methods From March to April 2022, 374 infection control nurses from 205 secondary and above medical institutions in Henan Province were chosen by convenience sampling, questionnaires about general information and core competence of infection control nurses were adopted for investigation. Results The total score of the core competence of infection control nurses was (279.90±29.28), the average scores of each dimension ranging from high to low were infection control knowledge and skill training ability (4.35±0.47), organization and cooperation ability (4.26±0.47), healthcare-associated infection (HAI) prevention and control ability (4.18±0.44), HAI risk prediction ability (4.01±0.49), and infection control professional development ability (3.94±0.53). Univariate analysis showed that there were significant differences in the scores of each dimension of core competence among nurses of different ages, grades of work units, educational background, professional titles, years of infection management and whether participated in infection academic conferences inside and outside the province every year (all P < 0.05). Multiple linear stepwise regression analysis result showed that the grades of work units, professional titles, years of infection management and whether participated in infection academic conferences inside and outside the province every year entered the regression equation, which could explain the 13.8% variability of core competence. Conclusion The core competence of infection control nurses in Henan Province is above the medium level, and there is still much room for improvement in the ability of predicting the risk of HAI and the ability of professional develop-ment of infection control, it is suggested to strengthen the training of these abilities and provide corresponding policy support.