Prior to pathological changes becoming apparent in any disease, the component and amount of intracellular proteins may undergo alteration. Thus, monitoring of proteins may be used to screen indicators in order to identify prognostic markers. The aim of this study was to investigate the feasibility of identification of serum biomarkers for lung cancer using protein mass spectrometry. Surface-enhanced laser desorption/ionization (SELDI) and weak cation exchange 2 (WCX2) protein chip array were employed for protein profiling of the sera of 17 healthy rabbits and 23 cancer‑bearing rabbits, of which 15 developed cancer in the lung (cancer group) and 8 developed lung cancer in the follow-up period (pre-cancer group). Data were obtained using a PBSII-C protein chip reader and analyzed using Biomarker Wizard and Proteinchip 3.1 software. Compared with the healthy rabbits, a total of 5 biomarkers were identified to be differentially expressed among 32 proteins screened from the sera in the cancer group and the pre-cancer group (P<0.05): 3 of the 5 biomarkers were upregulated and 2 were downregulated. Protein mass spectro-metry can be used to identify specific molecules closely correlated with the progression of lung cancer and, thus, this method may become an effective tool for the early diagnosis or prediction of lung cancer.