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The present study was designed to develop a sensitive and selective high performance liquid chromatography-tandem mass spectrometric method for the determination of Camellianin A in HepG2 cells.The extraction of Camellianin A was achieved using 15％ trichloroacetic acid and then separated on a C18 column interfaced with a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode.The mobile phase was consisted of methanol-water (0.1％ formic acid) (55:45,V/ V).The total run time was 5.0 min.The method was linear in the concentration range of 0.25-250.0 ng·mL-1.The lower limit of quantification was 0.25 ng·mL-1.The intra-and inter-day relative standard deviations of entire concentration range were less than 9.3％.The proposed HPLC-MS/MS method was successfully applied to detect the intracellular concentration of Camellianin A in HepG2 cells.