Rapid mass spectrometry analysis of protein in the solution sample was carried out by using a charged bubble extraction ionization device. In this work, experimental parameters including gases ( N2 and CO2 ) , bubble path length, voltage, and gas pressure on the charged bubble extraction ionization of lysozyme were investigated. Under the optimum experimental parameters including CO2 as extraction gas, bubble path length of 32 cm, solution voltage of 2 kV and gas pressure of 0. 05 MPa, this method was successfully used for the protein detection with the limits of detection of 1 ×10-8 mol/L in water solution and 1 ×10-7 mol/L in diluted urine (200 times in ultrapure water) . In addition, the limit of detection of 1 ×10-5 mol/L in undiluted urine was obtained with a urine volume of 6 mL at 2 kV voltage and 0. 06 MPa gas pressure. By comparing the desalting effects in charged bubble extractive ionization mass spectrometry and ESI-MS, it was found that the bubble charged extraction ionization method could obtain a wider and lower charge state distribution of protein ions, and had higher tolerance ability when facing non-volatile inorganic salts. Off-line study of the collected catalase after charged bubble extraction showed that 53. 9% enzyme activity was remained, which indicated that the proposed method was a soft ionization method. The method had merits including no sample pretreatment, no chemical reagent contamination and high speed, showing potential application to mass spectrometry analysis of protein components in solution. Therefore, this study provided a new method for mass spectrometry analysis of biological protein samples.