This research investigated the dynamics of antibiotic resistance in Salmonella and the epidemiology of Salmonella infection in children. These data can aid in the prevention and control of the Salmonella epidemic and the diagnosis and treatment of salmonellosis. Methods: In this study, we retrospectively reviewed and analysed data regarding epidemiology, clinical symptoms, Salmonella serotypes, and antibiotic resistance from the medical records of patients with Salmonella infections in Hangzhou Children's Hospital from April 2006 to December 2021. Results: A total of 2099 Salmonella isolates were identified during the 16-year study period, and 98.6% (2069) of the isolates were isolated from stool. About 84.5% (1773/2099) of the total Salmonella isolates were detected from May to October. The median age of the 2099 children with Salmonella infection was 1.4 years (17 months) (IQR: 0.9-2.8 years). In 1572 (74.9%) patients, the course of the disease was limited to uncomplicated gastroenteritis. S. Typhimurium (805/2099, 38.4%) was predominant, followed by S. Enteritidis (290/2099, 13.8%). The total number of serotypes and the number of less common serotypes are increasing. Nontyphoid Salmonella that cause invasive infections, including S. Typhimurium, S. Stanley, and S. Choleraesuis, accounted for 60.0% (18/30). The Salmonella strains were resistant to ampicillin, ampicillin-sulbactam, trimethoprim-sulfamethoxazole, ceftriaxone, and ciprofloxacin at percentages of 71.5%, 51.5%, 36.5%, 22.4%, and 14.7%, respectively. No imipenem-resistant strains were identified. 24.8% of the isolates exhibited multidrug resistance (MDR). Conclusion: S. typhimurium and S. enteritidis were the dominant serotypes in children (<2 years) with salmonella-infected arrhoea in Hangzhou, China. Ongoing serotype monitoring should be necessitated and dynamic changes in serotypes should be carefully examined to prevent the sudden outbreak of foodborne illness. Salmonella exhibits a higher rate of resistance to common antibiotics, and the risk of multidrug resistance should not be ignored. Therefore, clinicians should administer antibiotics judiciously according to the results of drug sensitivity tests.