Background/Aims: Hepatocellular carcinoma (HCC) is a highly malignant tumor, and its prognosis is very poor. It has been reported that small HCC possess most characteristics of early-HCC, and proteomic strategies has been widely used to study tumor biomarkers. We put forward new data reported about small HCC in order to screen potential biomarker for diagnosis of early-HCC. Methods: Ten pairs of tissues from HBV-infected small HCC patients were collected and treated with protein extraction. The extracted proteins were well resolved by two-dimensional electrophoresis (2-DE), and these HCC-associated proteins were identified by MALDI-TOF/TOF MS following image analysis. Results: 15 up-regulated and 3 down-regulated unique proteins were identified. Oxidoreductase and 3 of 5 metabolism associated proteins were increased, whereas 2 of 5 metabolism associated proteins were decreased in HCC samples. Finally, the overexpression of carbonyl reductase 1 (CBR1) and HSP27 in HCC tissues was confirmed by Real-time PCR and then by Western blot in 10 HCC samples, suggesting their potential as protein tumor markers. Conclusion: we concisely profiled proteomic alterations in small HCC tissues.CBR1 and HSP27 may be potential marker for early- HCC.