Objective To understand the epidemic characteristics and drug resistance of Salmonella I4, [5], 12∶I∶- in Maoming City. Methods Salmonella I4, [5], 12∶I∶- were identified by serological method, and then antibiotic sensitivity of isolated Salmonella I4, [5], 12∶I∶ - was tested by broth microdilution method. Results Among 476 strains of Salmonella from patients' feces, 143 strains of Salmonella I4, [5], 12∶I∶- were detected, and the detection rate was 33.81%. The feces of patients were mainly from infants <3 years old, the peak period mainly occurred from June to August. The rate of resistance to doxycycline was the highest (97.90%,140/143), followed by tetracycline (95.10%,136/143), sulfamethoxazole (93.71%,134/143), ampicillin (90.91%,130/143), streptomycin (86.71%,124/143), minocycline(83.22%,119/143), ampicillin/sulbactam (58.74%,84/143), chloramphenicol (58.74%,84/143) and sulfamethoxazole/trimethoprim (53.85%,77/143). Amikacin and meropenem were the most sensitive antibiotics, and no drug-resistant strains were found, followed by polymyxin B(99.30%,142/143), imipenem (99.30%,142/143), cefoxitin (97.20%,139/143), colistin (93.01%,133/143), ceftazidime(92.31%,132/143),azithromycin (92.31%,132/143), cefotaxime (81.82%,117/143), cefepime(79.72%,114/143)and aztreonam (79.72%,114/143). 97 kinds of drug resistance spectrum were identified, and the multi drug resistance rate was 100.00%. Conclusion Salmonella I4, [5], 12∶I∶- infection rate in infants is high, drug resistance is serious, and it is harmful to infants. It is necessary to expand the scope of sentinel hospitals and strengthen the surveillance of Salmonella, especially Salmonella I4, [5], 12∶I∶-. Salmonella I4, [5], 12∶I∶- was more sensitive to carbapenems and the second, third and fourth generation of cephalosporins which could be used as the first choice for treatment.