Purpose: Our recent comparative oncogenomic analysis in mouse model has identified YAP (Yes associated protein) as a novel oncogene in HCC. However, its clinical significance is unknown. In this study, we aimed to investigate the clinical values of YAP as an independent prognostic marker in HCC. Experimental Design: A total of 177 HCC cases with retrospective clinicopathologic and follow-up data were recruited in this study. Both tumor and adjacent non-tumor tissues were examined for immunoreactivity of YAP expression by immunohistochemistry. Clinicopathologic features and YAP expression were investigated with Pearson 2 test. HCC-specific disease free survival and overall survival with YAP expression were analyzed by Kaplan-Meier curves and Log-rank test. Cox regression was used to test the independence and magnitude of the effects. Results: YAP was found over-expressed in HCC (62.1%) with nuclear expression pattern. Positive YAP immunoreactivity was significantly correlated with worse tumor differentiation grade (P=0.021) and high serum alpha-fetoprotein (AFP) level >400 ng/ml (P<0.001). Kaplan-Meier plot and Cox Regression showed that YAP was an independent predictor for HCC-specific disease free survival (hazard ratio, 1.653; 95% CI, 1.084-2.522; P=0.02) and overall survival (hazard ratio, 2.226; 95% CI, 1.312-3.778; P=0.003). Conclusions: YAP expression in HCC is correlated with tumor differentiation and serum AFP level. It served as an independent prognostic marker for HCC. Background: Integrative analysis of global protein and mRNA expression patterns could help researchers to understand cancer cell physiology without the need of any prior hypothesis. Methods: We used a 2D-PAGE approach to profile and compared the global protein expression profiles of hepatitis B virus-related HCC tissues, adjacent non-tumor liver tissues, normal liver tissues and HCC cell lines. Subsequently, we established the bioinformatic tools for integrative analysis of gene expression and protein expression data. We compared the dysregulated protein list and the dysregulated gene lists obtained by meta-analysis of microarray gene expression data from 6 research centers in different countries. Results: We identified 66 proteins dysregulated in HCC. Hierarchical clustering analysis revealed that there was a progressive change of protein expression patterns from normal liver, adjacent non-tumor liver tissues, HCC tissue, then to HCC cell lines. According to the biological functions, the differential proteins could be classified into various groups, including heat shock protein, chaperone, kinase substrate, cell signaling, apoptosis regulation, transcription regulation, free-radical scavenger and metabolic enzyme. Ontology analysis of the genes with consistent dysregulations at both mRNA and protein levels identified specific pathways down-regulated during the progression of HCC. The inhibition of those pathways provides new insights in the hepatcarcinogensis and treatment strategies. Results: In pre-S/surface regions, HCC patients had higher frequencies of pre-S deletions, amino acid substitutions at codon 4, 7, and 81 in pre-S1 genes, at the start codon in pre-S2 genes, and at codon 68 in surface genes. But they had a lower frequency of amino acid substitution at codon 2 in pre-S2 genes than those without HCC. In BCP/precore regions, HCC patients had higher frequencies of C or G1753, A1762/T1764, T1846, and A1899 than those without HCC. Multivariate analysis showed that pre-S deletions, I68T in surface gene, T1762/A1764, and A1899 were independent factors for HCC. The HBV with a complex mutation pattern (pre-S deletion, T1762/A1764, and A1899) rather than a single mutation was associated with HCC. Patients with combined mutations of T1762/A1764 and pre-S deletion, T1762/A1764 and A1899, pre-S deletions and A1899, and T1762/A1764, pre-S deletions and A1899 had a 7.81, 7.7, 7.0, and 16.88 fold increased risk of HCC, respectively, compared to patients with wild-type at both or three genomic regions. Conclusions: Pre-S deletions, I68T in surface gene, T1762/A1764, and A1899 were independent factors for HCC. Combination of these viral mutations appeared increasing HCC risks.