Bisphenol F (BPF) is widely used in the plastic manufacturing industry as a replacement for bisphenol A (BPA) because BPF and BPA have similar structures and comparable properties. However, BPF is ubiquitously present in the environment and has higher toxicity to humans. This study is the first to report BPF degradation using the white-rot fungus Phanerochaete sordida YK-624 under ligninolytic conditions (pH=4.5, 30 °C). P. sordida YK-624 almost completely degraded BPF within 4 days. Moreover, functional genes involved in BPF degradation were detected by RNA-Seq. Metabolic processes and peroxidases were enriched by GO analysis, and the metabolic pathway was enriched according to the KEGG pathway analysis. These results suggested that P. sordida YK-624 could secrete higher levels of ligninolytic enzymes lignin peroxidase (LiP) and manganese peroxidase (MnP) for BPF degradation. The results indicated that LiPs and MnPs are important for BPF degradation and cytochrome P450s play a small role. Furthermore, reliability of the RNA-Seq results was validated by qRT-PCR.