Background Improving feed efficiency is the most important goal for modern animal production. The regulatory mechanisms of controlling feed efficiency traits are extremely complex and include the functions related to host genetics and gut microbiota. Short-chain fatty acids (SCFAs), as significant metabolites of microbiota, could be used to refine the combined effect of host genetics and gut microbiota. However, the association of SCFAs with the gut microbiota and host genetics for regulating feed efficiency is far from understood. Results In this study, we examined host genome sequence, microbial data and SCFA concentration of caecal chyme in 300 broilers. The SNP-based heritability analysis found that the SCFA concentrations had moderate to high heritability (h2 = 0.183 ~ 0.401). Genome-wide association studies (GWAS) showed that four out of seven SCFAs had significant associations with genome variants. One locus (gga4: 29414391–29417189) was significantly associated with propionate, locating near or inside the genes MAML3, SETD7 and MGST2, and had a modest effect on feed efficiency traits and the microbiota. The genetic effect of the top SNP explained 8.43% phenotype of propionate. Individuals with genotype AA had significantly different propionate concentrations (0.074 vs. 0.131 ug/mg), feed efficiency (FCR: 1.658 vs. 1.685), and relative abundance of 14 taxa compared to those with the GG genotype. Christensenellaceae and Christensenellaceae_R-7_group were identified being associated with feed efficiency, propionate concentration and top SNP genotypes, and they were found to be lipid metabolism-related. Individuals with a higher caecal abundance of these taxa showed better feed efficiency and lower concentrations of caecal SCFAs. Conclusion Our study concluded that host genetic variation could affect the regulation of caecal microbially-derived SCFAs, which plays a role in host feed efficiency traits. The caecal taxa Christensenellaceae and Christensenellaceae_R-7_group were identified as representative taxa contributing to the combined effect of host genetics and SCFAs on chicken feed efficiency. These findings proved strong evidence of the combined effect of host genetics and gut microbial SCFAs in regulating feed efficiency traits.