To investigate the impact of 3 single nucleotide polymorphisms (SNPs) in the interleukin-6 (IL-6) gene and their interaction on susceptibility to frailty in the elderly in rural areas of China Bai nationality. Taking the Bai people in Dali, China as the research object, and according to the frailty phenotype scale, there were 2 groups: frail and non-frail. Basic information about the study participants was gathered using a questionnaire. Clinical biochemical indices were also evaluated and the Sanger method was used to identify the sequences of the IL-6 gene loci at rs1524107, rs1800796, and rs10499563. SHEsis online software was used to analyze the linkage disequilibrium of IL-6 gene sites and the relationship between haploids and frailty. The MDR software was used to analyze the 3 sites and their interactions. Among 231 rural Bai elderly people, 63 (27.3%) were frail and 168 (72.7%) were non-frail. The SNPs of rs1524107, rs1800796, and rs10499563 in the IL-6 gene were not associated with the occurrence of frailty, nor were they associated with clinical indicators such as grip strength and gait speed. After adjusting for age and gender, there was no significant difference in the distribution of the 3 genetic models composed of the 3 SNPs between frail and non-frail populations (all P > .05). The 3 haplotypes were not associated with the occurrence of frailty, and the interaction between the 3 loci was not associated with the susceptibility to frailty. The SNP of rs1524107, rs1800796, and rs10499563 sites of IL-6 gene may not be related to frailty susceptibility in Dali Bai people. Differences in frailty mechanisms among other populations at the gene level, which are of enormous significance for the prevention and treatment of frailty, require further research with larger samples and more gene loci.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.