Objective To study the prevalence and antimicrobial resistance characteristics of Salmonella enterica serovar typhimurium（S. typhimurium）and monophasic S. typhimurium from clinical patients and food in Henan Province from 2015 to 2022.Methods Three hundred and ninety-nine strains of Salmonella from food and clinical patients in Henan Province were serotyped according to the Kauffmann White scheme by slide agglutination and multiplex real-time PCR method. Microbroth dilution method was used to test antimicrobial resistance of S. typhimurium. Statistical analysis was carried out using Chi-square test.Results Three hundred and ninety-nine strain were composed of two hundred twenty-five monophasic S. typhimurium （56.39%） and one hundred seventy-four S. typhimurium. The imipenem and trimethoprim/ sulfamethoxazole resistant isolates were found since 2017. The antimicrobial resistance rate of two Salmonella strains to ampicillin， chloramphenicol and tetracycline was higher， reaching more than 50%. The antimicrobial resistance rate of monophasic S. typhimurium to ampicillin and gentamicin was significantly higher than that of S. typhimurium （P<0.05）. The resistance rate of S. typhimurium to cefazolin was significantly higher than that of monophasic S. typhimurium （P<0.05）. Two serotypes of S. typhimurium were resistant to over 60% of three classes or more antimicrobial agents. The common multiple dominant antimicrobial resistance spectrum was ampicillin-chloramphenicol-trimethoprim/sulfamethoxazole-tetracycline pattern.Conclusion Monophasic S. typhimurium had replaced S. typhimurium as predominant serotype in clinical patients in Henan Province. Two serotypes of S. typhimurium strains are generally antimicrobial resistant and the multi-antimicrobial resistance patterns serious. In order to make effective interventions and reduce the spread of S. typhimurium. The study results suggest that the detection rate of foodborn S. typhimurium should be strengthen as well as the antimicrobial resistance of monophasic S. typhimurium.