Objective Establishing the database of food-borne Salmonella typhimurium 1,4,[5],12∶i∶- and monophasic variant in Guangxi Zhuang Autonomous Region by investigating the drug resistance and molecular typing characteristics of the isolates in 2018. Methods 124 strains of S.1,4,[5],12∶i∶- from clinic samples and food samples were tested for drug sensitivity by minimum inhibitory concentration (MIC), and molecular typing by pulsed field gel electrophoresis (PFGE). Results One hundred and twenty four strains of S.1,4,[5],12∶i∶- were all sensitive to imipenem, but resistant to the other 13 antibiotics at different levels. The resistance rate to tetracycline was the highest (96.8%, 120/124), followed by ampicillin (95.2%, 118/124). Multidrug resistant (MDR) rate was 26.6% (33/124), and 47.1% S.1,4,[5],12∶i∶- isolates were multi-resistant to ACSuT. The S.1,4,[5],12∶i∶- strains were differentiated into 104 Xba I PFGE patterns with similarity of 72.9%-100%, and the dominant patterns were JPXX01.GX0114 (5 isolates) and JPXX01.GX0294 (4 isolates), all of which came from foodborne disease surveillance. Conclusion The result indicated that the S.1,4,[5],12∶i∶- isolates in Guangxi were highly resistant to penicillins and tetracyclines and drug resistance situation was not optimistic, S.1,4,[5],12∶i∶- PFGE pattern were highly sporadic. It is necessary to trace the molecular origin of the isolated strains on time, which can improve ability to identify potential food-borne S.1,4,[5],12∶i∶- outbreak events in sporadic cases.