Objective To search the specific biomarkers in serum of patients with silicosis for early diagnosis. Methods Surface enhanced laser desorption ionization-time of flight-mass spectrometry (SELDI-TOF-MS) was used to search the specific biomarkers in serum samples from 60 silica-exposed workers (20 with no silicosis served as 0 group, 20 with suspected silicosis as 0+ group and 20 with stage I silicosis as stage I group), and 20 healthy men with no silica exposure as control. Serum samples were analyzed using the new generation of weak cationic exchange chip (CM10, Ciphergen Biosystems, America) and the protein fingerprint automatically collected using ProteinChip Biology System (PBSII-C) instrumentation. The data were analyzed by Ciphergen ProteinChip and BioMarker Wizard software. Results Compared with control group, ten biomarkers were differentially expressed among all the silica-exposed workers (P