▎ 摘　　要

Graphene has attracted enormous attention due to its unique and novel properties, showing great potential in different fields including biomedical engineering, tissue engineering, and biosensors. Thus, systematic investigation of the cytotoxicity of graphene is crucial for further clinical use. However, there have been numerous contradictory reported results about the biocompatibility and cytotoxicity of graphene based on conventional in vitro toxicity test methods. We herein report a metabolomics approach to investigate the metabolic responses on graphene treated HepG2. Multivariate data analytic approaches reflected the significant difference in metabolic profiles between graphene-treated groups and the control group. According to the results of analysis of variance (ANOVA), twelve metabolites were detected as potential biomarkers. Moreover, three KEGG pathways including arginine and proline metabolism, purine metabolism, and glycophospholipid metabolism were identified. Our findings demonstrated that metabolomics would be an efficient platform to understand the molecular mechanism of cytotoxicity of graphene.