The common walnut (or Persian walnut), Juglans regia L., is an economically important temperate tree species valued for both its edible nut and high-quality wood. F-box gene family members are involved in plant development, which includes regulating plant development, reproduction, cellular protein degradation, response to biotic and abiotic stresses, and flowering. However, in common walnut (J. regia), there are no reports about the F-box gene family. Here, we report a genome-wide identification of J. regia F-box genes and analyze their phylogeny, duplication, microRNA, pathway, and transcriptional expression profile. In this study, 74 F-box genes were identified and clustered into three groups based on phylogenetic analysis and eight subfamilies based on special domains in common walnut. These common walnut F-box genes are distributed on 31 different pseudo-chromosomes. The gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and microRNA profiles showed that the F-box gene family might play a critical role in the flowering of common walnut. The expressions were significantly higher in female flowers and male flowers compared with leaf and hull tissues at a transcriptome level. The results revealed that the expressions of the F-box gene in female flowers were positively correlated with male flowers, but there was no correlation between any other tissue combinations in common walnut. Our results provided insight into the general characteristics of the F-box genes in common walnut.