Abstract: Objective To look for specific tuberculosis (TB)-related serum proteins and further to discover new serological diagnostic markers of TB by comparison of the serum protein mass spectra between TB patients and healthy persons. Methods The serum proteins from 62 healthy controls (control group) and 117 TB patients (TB group),including 54 cases with bacterium-positive pulmonary TB (bacterium-positive group) and 45 cases with bacterium-negative pulmonary TB (bacterium-negative group) and 18 cases with extra-pulmonary TB (extra-pulmonary group), were detected using the WCX protein-chip and the surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) technology. Then the detected data of serum protein mass spectra were analyzed by ClinProTools Software to find the different proteins. Results There were 19, 14, 26 and 30 significantly different protein peaks respectively in bacterium-positive group vs control group, bacterium- negative group vs control group, extra-pulmonary group vs control group, and TB group vs control group.There were 11, 9, 15 and 15 protein respectively to be up-regulated expression in each TB group. Four protein peaks at 1060、1944、2081 and 3954 m/z differentially existed between all of TB groups and control group, in which 1060 m/z protein was down-regulated expressd in all of TB groups. Conclusion The serum protein spectra had difference between TB patients and healthy persons. The new TB serological diagnostic markers need be further studied to be confirmed.