Background: Feed conversion ratio (FCR) is an important productive trait that largely affects profits in pig industry. Elucidating the genetic mechanisms underpinning the FCR potentially promote the efficiencies of improving FCR through artificial selection. In this study, we integrated a genome-wide association study (GWAS) with transcriptome analyses in different tissues in Yorkshire pigs (YY), aimed at identifying key genes and signaling pathways significantly associated with FCR.Results: A total of 61 significant single nucleotide polymorphism (SNPs) were detected by GWAS in YY. All of these SNPs are located on porcine chromosome (SSC) 5 and the covered region was considered as a quantitative trait locus (QTL) region for FCR. Some genes that distributed around these significant SNPs were considered as the candidates for regulating FCR, including TPH2, FAR2, IRAK3, YARS2, GRIP1, FRS2, CNOT2 and TRHDE. According to the transcriptome analyses in hypothalamus, TPH2 exhibits abilities of regulating the intestinal motility by a serotonergic synapse and an oxytocin signaling pathway. In addition, GRIP1 is involved in a glutamatergic and GABAergic signaling pathway, which regulates FCR through affecting the appetite in pigs. Moreover, GRIP1, FRS2, CNOT2, TRHDE regulates the metabolism in various tissues by a thyroid hormone signaling pathway.Conclusions: Synthesizes results from GWAS and transcriptome analyses, TPH2, GRIP1, FRS2, TRHDE, CNOT2 genes were considered as candidate genes for regulating FCR in Yorkshire pigs. These findings help to improve the understandings of the genetic mechanism of FCR and potentially optimize the design of breeding schemes.