Pharmacogenomic studies of different ethnic or racial groups have been used to develop personalized therapies specific to subjects. This study aimed to identify the distribution differences of very important pharmacogenetic (VIP) variants between the Lisu population from southwestern China and other ethnic groups.Eighty VIP variants in 37 genes were selected from the pharmacogenomic knowledge base (PharmGKB), and compared with genotype data of the Lisu population then compared with other 11 populations from the HapMap dataset and previously published data including Miao, Li, Deng, Sherpa, Lhoba, Tibetan, Kirghiz, Tajik, Mongol, Shaanxi Han ethnic, and Uygur populations.VDR rs1540339, MTHFR rs1801131, P2RY1 rs701265, and PTGS2 rs689466 were significantly different between Lisu and 11 HapMap populations. ANKK1 rs1800497 was the least statistical significant locus among selected single nucleotide polymorphisms. In addition, genetic background of Lisu was strongly closest to Shaanxi Han ethnic cohort, and followed by Chinese in metropolitan Denver population based on population structure and F-statistics analyses.Our results showed significant interethnic differences between Lisu and other populations, which will give useful information for prospective studies and better individualized treatments.