Synthetic cathinones, which are a group of β-keto analogs of phenethylamine, have been reported as the most emerging new psychoactive substances in the past decade. The quantity and variety of synthetic cathinones have continued to increase, which poses considerable risks to public health and social security. In this study, an analytical method based on liquid-liquid extraction combined with gas chromatography-mass spectrometry (GC-MS) was carried out and applied in the simultaneous determination of 19 synthetic cathinones in tablets. Under the optimized conditions of liquid-liquid extraction, the determination of synthetic cathinones in tablets was carried out with GCMS. Good linear relationships of 19 synthetic cathinones were obtained in the range of 5–20 µg/L with the correlation coefficients (r) ranging from 0.9901 to 0.9968, the limits of detection were in the range between 1.2 and 1.5 µg/mL, and the limits of quantitation were between 3.9 and 5.0 µg/mL. The results show the advantages of the approach in the determination of synthetic cathinones in tablets with fast detection, high efficiency and sensitivity. The practical application indicated that this method could provide scientific basis for the determination of drugs of abuse in other laboratories.