Abstract: Objective: To investigate the expression characteristics of 3-hydroxybutyrate dehydrogenase 2 (BDH2) and macrophage migration inhibitory factor (MIF) in nasopharyngeal carcinoma (NPC) and their impact on macrophage infiltration in the tumor immune microenvironment. Methods: 5-8F cells were transfected with BDH2 overexpression plasmids, and the transcription level of BDH2 was detected by quantitative real-time polymerase chain reaction (qPCR). Western blotting was used to verify the expression differences of BDH2 and MIF. Enzyme-linked immunosorbent assay (ELISA) and colorimetric method were performed to detect the expression levels of MIF and acetoacetate in cells. Immunohistochemistry (IHC) was used to analyze the expression levels of BDH2 and MIF in NPC and normal nasopharyngeal epithelium tissues. Serial section staining and correlation analysis were used to assess the relationship between MIF expression and M1 and M2 macrophage infiltration. Results: Overexpression of BDH2 significantly increased the intracellular levels of acetoacetate in 5-8F cells (P＜0.01), and MIF expression was downregulated. GEO database and IHC results showed that BDH2 expression was significantly downregulated in NPC tissues (P＜0.0001) and MIF expression was significantly upregulated (P＜0.01). Serial section analysis revealed that NPC tissues with high MIF expression had reduced M1 macrophage infiltration (P＜0.0001). Conclusion: The BDH2-MIF axis in NPC regulates the immune microenvironment by inhibiting M1 macrophage infiltration and may serve as a potential therapeutic target for NPC.