Objective To study the serotype distribution and drug resistance of Salmonella isolates from diarrhea cases in Zhongshan City from 2016 to 2017. Methods Serotype of 540 strains of Salmonella spp. was determined from diarrhea cases monitored and isolated in Zhongshan City from 2016 to 2017. Furthermore, broth microdilution method was used for drug sensitivity test. Results 540 Salmonella strains isolated in Zhongshan City from 2016 to 2017 covered 59 serotypes and there were 22 common serotypes. Among them, the dominant serotypes were monophasic variant of S.Typhimurium (41.9%, 226/540), S.Enteritidis (13.1%, 71/540), S.Typhimurium (9.3%, 50/540) and S.Stanley (9.3%, 50/540), accounting for 73.5%(397/540) of the total strains. Drug susceptibility test showed that the resistance rate of Salmonella to ampicillin, ampicillin/sulbactam and tetracycline was higher than 50.0%. However, resistance to cephalosporins varies considerably. The drug resistance rates of cefazolin, cefotaxime, ceftazidime and cefoxitin were 34.1%(184/540), 25.7%(139/540), 12.2%(66/540) and 1.5%(8/540), respectively. In addition, all Salmonella strains were sensitive to imipenem, while S.Stanley was sensitive to six antibiotics. The multiple drug resistance rate was 65.4%(353/540). The multidrug resistance rates of the 4 dominant serotypes of monophasic variant of S.Typhimurium, S.Enteritidis, S.Typhimurium and S.Stanley were 82.7%(187/226), 56.3%(40/71), 72.0%(36/50) and 16.0%(8/50) respectively. And there was significant difference in the rate of multiple drug resistance (P<0.05).Conclusion Salmonella isolates from diarrhea cases in Zhongshan City show biodiversity. Salmonella has a high rate of multiple drug resistance, among which monophasic variant of S.Typhimurium is the most serious strain, which should be paid attention to.