Inflammatory response is involved in the development of facial neuritis. The aim of our study is to explore the role of mitophagy in facial nerve damage induced by tumor necrosis factor α (TNFα). Our results indicated that TNFα induced SH-SY5Y cell apoptosis in a dose-dependent manner. Besides, TNFα treatment also suppressed mitophagy by reducing the expression of BCL2 interacting protein 3 (Bnip3). Overexpression of Bnip3 under sustained SH-SY5Y cell viability in the setting of TNFα-mediated inflammation injury. At the molecular levels, Bnip3 overexpression maintained mitochondrial function via preserving mitochondrial membrane potential, reducing cytochrome-c leakage and inhibiting mitochondrial permeability transition pore opening. Functional studies have suggested that microRNA-145 (miR-145) was an upstream regulator of Bnip3-dependent mitophagy. MiR-145 inhibited Bnip3 transcription and expression, leading to mitophagy inhibition. In contrast, inhibition of miR-145 reversed mitophagy activity and subsequently promoted SH-SY5Y cell survival in the context of TNFα-mediated inflammation injury. Altogether, our data identified Bnip3-dependent mitophagy as one of the defensive mechanisms to sustain mitochondrial homeostasis and SH-SY5Y cell survival. Besides, miR-145/Bnip3/mitophagy axis may be considered as a potential target for the treatment of facial neuritis in clinical practice.