Uterine fibroid is one of the most prevalent benign tumors in women, with high socioeconomic costs. Although genome-wide association studies (GWAS) have identified several loci associated with uterine fibroid risks, they could not successfully interpret the biological effects of genomic variants at the gene expression levels. To prioritize uterine fibroid susceptibility genes that are biologically interpretable, we conducted a transcriptome-wide association study (TWAS) by integrating GWAS data of uterine fibroid and expression quantitative loci data. We identified nine significant TWAS genes including two novel genes, RP11-282O18.3 and KBTBD7, which may be causal genes for uterine fibroid. We conducted functional enrichment network analyses using the TWAS results to investigate the biological pathways in which the overall TWAS genes were involved. The results demonstrated the immune system process to be a key pathway in uterine fibroid pathogenesis. Finally, we carried out chemical-gene interaction analyses using the TWAS results and the comparative toxicogenomics database to determine the potential risk chemicals for uterine fibroid. We identified five toxic chemicals that were significantly associated with uterine fibroid TWAS genes, suggesting that they may be implicated in the pathogenesis of uterine fibroid. In this study, we performed an integrative analysis covering the broad application of bioinformatics approaches. Our study may provide a deeper understanding of uterine fibroid etiologies and informative notifications about potential risk chemicals for uterine fibroid.