Salmonella enterica serovar Indiana ( Indiana) is an extremely expanded foodborne pathogen in China in recent years. This study aimed to elucidate the national prevalence and phylogenomic characterization of this pathogen in China. Among 5, 287 serotyped Salmonella isolates collected during 2002 to 2018, 466 Indiana isolates were found in 15 provinces, and 407 were identified to be ST17, and the rest were ST2040. Among 407 ST17 isolates, 372 (91.4%) were multidrug resistant, and 366 (89.9%) were resistant to ciprofloxacin, 235 (57.7%) were further resistant to ceftriaxone. Phylogenomic analysis revealed that ST17 isolates were classified into four clades (I, II, III and IV), which appeared in international clonal dissemination. ST17 isolates from China fell into Clade IV with part of isolates from the United Kingdom, the United States, South Korea, and Thailand, suggesting their close genetic relationship. Mutations in quinolone resistance-determining regions (QRDR) of GyrA and ParC, and plasmid-mediated quinolone resistance (PMQR) genes (6')-Ib-cr, AB, and S as well as extended spectrum β-lactamases (ESBL) genes , , and in isolates from Clade IV were much higher than those from other three clades. Various subtypes (, , , , and ) with IS, IS, IS, and IS were found in ST17 isolates, especially Tn containing ΔIS--IS in P1-like bacteriophage plasmids. These findings on the prevalent and genomic characterization for the . Indiana multidrug-resistant ST17 clone in China, which have not been reported yet, provide valuable insights into the potential risk of this high-resistant clone. Fluoroquinolones and cephalosporins are the primary choices for severe salmonellosis treatment. Indiana has become one of the most prevalent serovars in breeding poultry and poultry meats in China in recent years. ST17 was recognized as the leading epidemiological importance in Indiana because of its high-level resistance to the most of common antibiotics, including ciprofloxacin and ceftriaxone. However, the prevalence and phylogenomic characterization of ST17 isolates are unclear. Here, we did a retrospective screening on a large scale for Indiana in China, and performed its phylogenomic analysis. It was found that ST17 isolates had extensive spread in 15 provinces of China and became a multidrug-resistant clone. The international spread of the ST17 isolates was observed among several countries, especially China, the United Kingdom, and the United States. Our study emphasized the importance of surveillance of a high-resistant Indiana ST17 clone to combat its threat to public health.