Objective: To analyze the serotypes and drug resistance of Salmonella in patients with diarrhea in Huidong area so as to provide reference for formulating prevention and treatment measures and guiding clinical medication. Methods: The bacterial culture results of stool samples from 955 patients with diarrhea diagnosed and treated in hospitals from 2018 to 2020 were collected, and the serotypes and drug resistance of Salmonella isolates were analyzed. Results: A total of 61 strains of Salmonella were detected in the stool samples from 955 patients with diarrhea, and 12 serotypes were isolated (Salmonella typhimurium and Salmonella enteritidis were the main serotypes, accounting for 34.43% and 24.59%, respectively). The drug sensitivity results showed that the drug resistance rates of Salmonella to ampicillin, tetracycline and chloramphenicol were 88.52%, 72.13% and 55.74%, respectively. The sensitivity rates of Salmonella to the third generation cephalosporins were about 73.00%, to quinolones were about 95.00%, to carbapenem was 100.00%. There were 34 strains of Salmonella resistant to more than 3 kinds of antibacterials, and the multi-drug resistance rate was 55.74%. Conclusion: The serotypes of Salmonella in diarrhea patients in Huidong area are mainly typhus and enteritis which have strong drug resistance and serious multi-drug resistance. Therefore, drug resistance monitoring and prevention and treatment countermeasures should be actively carried out to guide clinical scientific drug use.