Abstract: 2,6-dimethylbenzenamine was determined as a genotoxic impurity in lidocaine hydrochloride injection, and 2-chloro-N-(2,6-dimethylphenyl) acetamide was determined as potential genotoxic impurity. An LC-MS/MS method was established to research the profiling of genotoxic impurities in active pharmaceutical ingredients (API), homemade preparation and reference preparation on column Agilent ZORBAX Eclipse Plus C₁₈(4.6 mm $\times$ 250 mm， 5 μm). The results show that in the homemade preparation the 2,6-dimethylbenzenamine and the 2-chloro-N-(2, 6-dimethylphenyl) acetamide may be degraded under oxidation condition and alkaline condition in addition to the introduction from API preparation process. This study provides guidance for genotoxic risk assessment and prescription process optimization of lidocaine hydrochloride.