The protein content in bone extract was abundant, and the nutrients in bone can be extracted through recycling to synthesize meat flavoring. In order to study the optimal Maillard process of thermal reaction chicken bone flavoring, and to obtain the chicken bone flavoring with rich meaty aroma and mellow taste, chicken bone extract was used as the raw material. The double enzyme of complex protease (ProtamexTM) and complex flavor protease (FlavourzymeTM) was used for hydrolysis, and the enzymatic hydrolysate was subjected to the Maillard heat-reaction. Through the preliminary experiments, four factors, such as the addition of hydrolyzed vegetable protein (HVP), the ratio of the addition of cysteine and its hydrochloride to the addition of reducing sugar (glucose, xylose), the thermal reaction time, and the thermal reaction temperature were taken for the single-factor experiment optimization. The sensory scores and the total weights of equivalent umami concentration were taken as the indexes to design the response surface experiments. The optimal thermal reaction conditions were HVP mass fraction of 6.5%, temperature of 106℃, time of 40min, mass ratio of cysteine and its hydrochloride to reducing sugars (glucose and xylose) of 1∶1, and the total weights of sensory score and equivalent umami concentration was 7.735. The volatile odor compounds were qualitatively and quantitatively detected by comprehensive two-dimensional gas chromatography-olfactometry-mass spectrometry. The volatile odor compounds with strong olfactory intensity were accurately and quantitatively analyzed, and the odor activity value (OAV) was calculated to identify the key aroma active compounds of the thermal reaction chicken bone flavoring under the optimized conditions. It was found that sulfur-containing compounds such as 2-methyl-3-furanethiol and furfuryl mercaptan and pyrazines such as 2,5-dimethyl-3-ethylpyrazine, 5-methyl-2-ethylpyrazine, and 2,3-diethyl-5-methylpyrazine were significantly increased in the thermal-reaction chicken bone flavoring compared to the chicken bone hydrolysate before the thermal reaction and the OAVs of these substances was greater than 1. The increase of these substances was the reason for the richness of meat aroma and aroma of thermal reaction chicken bone flavoring. It was hoped that this study could provide a theoretical basis for the industrialized production of thermal reaction chicken bone flavoring, and provide a reference idea for the utilization of animal husbandry by-products.