The study aimed to find novel effect biomarkers for occupational benzene exposure and chronic benzene poisoning (CBP), which might also provide clues to the mechanism of benzene toxicity.We performed a comparative serological proteome analysis between healthy control workers with no benzene exposure, workers with short-term benzene exposure, workers with long-term benzene exposure, and CBP patients using 2D-DIGE and MALDI-TOF-MS. Two of the differentially expressed proteins were then selected to be validated by immune turbidimetric analysis.A total of 10 proteins were found to be significantly altered between different groups. The identified deferentially expressed proteins were classified according to their molecular functions, biological processes, and protein classes. The alteration of 2 important serum proteins among them, apolipoprotein A-I and transthyretin, were further confirmed.Our findings suggest that the identified differential proteins could be used as biomarkers for occupational benzene exposure and CBP, and they may also help elucidate the mechanisms of benzene toxicity.