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Owing to its high porosity, specific surface area and three‐dimensional structure, three‐dimensional graphene (3D–C) is a promising scaffold material for tissue engineering, regenerative medicine as well as providing a more biologically relevant platform for living organisms in vivo studies. Recently, its differentiation effects on cells growth and anti‐inflammation properties have also been demonstrated. Here, we report a complete study of 3D–C as a fully adequate scaffold for tissue engineering and systematically analyze its biocompatibility and biodegradation mechanism. The metabolic activities of liver cells (HepG2 hepatocarcinoma cells) on 3D‐C are studied and our findings show that cell growth on 3D–C has high cell viability (> 90%), low lactate production (reduced by 300%) and its porous structure also provides an excellent oxygenation platform. 3D–C is also biodegradable via a 2‐step oxidative …