Hepatocellular carcinoma (HCC) is one of the most common human malignancies in the world. To identify the histological subtype-specific genes of HCC, we analyzed the gene expression profile of 10 HCC patients by means of cDNA microarray. We proposed a systematic approach for determining the discriminatory genes and revealing the biological phenomena of HCC with cDNA microarray data. First, normalization of cDNA microarray data was performed to reduce or minimize systematic variations. On the basis of the suitably normalized data, we identified specific genes involved in histological subtype of HCC. Two classification methods, Fisher's discriminant analysis (FDA) and support vector machine (SVM), were used to evaluate the reliability of the selected genes and discriminate the histological subtypes of HCC. This study may provide a clue for the needs of different chemotherapy and the reason for heterogeneity of the clinical responses according to histological subtypes.