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BACKGROUND: Chrysin (5,7-dihydroxyflavone) is a flavonol in many natural plant extracts. It has a wide range of therapeutic effects and is involved in inflammatory reactions in the body that can enhance osteoclast formation and lead to bone erosion. OBJECTIVE: To investigate the effects of chrysin on osteoclast differentiation and its protective effect on bone erosion in inflammatory and non-inflammatory environments. METHODS: RAW264.7 cells were selected as seed cells. First, the RAW264.7 cells were induced with receptor activator of nuclear factor kappa B ligand (50 μg/L) and macrophage colony-stimulating factor (25 μg/L) to generate osteoclasts. The cells were randomly divided into four groups according to chrysin concentration (0, 20, 40, and 60 μg/L). Second, lipopolysaccharide was used to simulate the inflammatory environment. RAW264.7 cells were induced by lipopolysaccharide to differentiate into osteoclasts, and the effect of different concentrations of chrysin (0, 20, 40, 60 μg/L) on osteoclast differentiation was observed in the same way. RESULTS AND CONCLUSION: Chrysin effectively inhibited osteoclast differentiation, with the maximum effect at 60 μg/L. Chrysin significantly inhibited the bone absorption function of osteoclasts, suggesting that chrysin has a protective effect on bone erosion caused by osteoclasts. Chrysin suppressed the protein and gene expression related to osteoclast differentiation by nuclear factor kappa B signaling pathway. Therefore, chrysin has an anti-inflammatory effect and it is also powerful to inhibit osteoclast differentiation in an inflammatory environment. [ABSTRACT FROM AUTHOR]