Abstract: Yellow rice wine is a typical Chinese wine, which is famous for nutritive value. The enzymes in the yeast produce tyramine, which influences the neurotransmission in the body. High level of tyramine concentration in human body will lead to alert, elevation of blood pressure and neurological disorders. Undoubtedly, the concentration of the tyramine should be analyzed and controlled. High performance liquid chromatography-mass spectrometry (HPLC/MS) is applied as the common method to analyze the tyramine in complex system with high sensitivity but complicated preprocessing and derivatization. In this paper, mass spectrometry method was developed for fast determination of tyramine in yellow rice wine. The laser desorption/laser post ionization mass spectrometry (L2MS) setup was built in house, and the selectivity of the tyramine in L2MS method can be explained by the principle of resonant two-photon ionization (R2PI). Solutions of tyramine at gradient concentrations were analyzed by L2MS (wavelengths of the desorption and post ionization laser are 532 nm and 266 nm, respectively), and the limit of detection (LOD) of tyramine was calculated. Compared with laser desorption ionization mass spectrometry (LDI/MS, wavelength of the laser is 532 nm), L2MS method obtained distinct molecular ion peak (m/z 137) with little interference peaks. Yellow rice wine sample was directly analyzed, the tyramine content of which was estimated using standard addition method. The signal of tyramine in the yellow rice wine was obvious and intensive. The mass spectra were analyzed and the fragmentation pathways of tyramine were discussed in detail. The LOD of tyramine in pure sample is 32 μg/L, and the concentration of the tyramine in yellow rice wine is about 68 mg/L. Poor signals were obtained by the electron spray ionization mass spectrometry (ESI-MS) because of quality discrimination and lack of the selectivity of tyramine. This method offers direct detection of the tyramine in the yellow rice wine without time-consuming sample preparation. Besides, simple and explicit mass spectra with excellent sign-to-noise ratio can be obtained. This method can be applicable for the selective determination of tyramine in various practical samples such as white spirit, grape wine and soybean sauce.