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Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignancies seen in Far East Asia but with a relatively lower incidence in the United States. Because of the variety of tumor characteristics, factors associated with prognosis and survival have been difficult to determine. Methods: 71 patients with HCC resected at an America institution were compared with 51 patients resected in Asia using clinical data analyses. These results and demographic data were then correlated with results from immunohistochemical staining of microarray sections for significance of prognostic and survival parameters. Results: When comparing the Asian and American, significant differences were found in expression of p53 and MDM2. Higher p53-positive staining was seen in the Asian group(P =0.04), while MDM2-positive staining was higher in the American group(P=0.0003)(in press). Survival rates of patients according to p53-positive or -negative status indicated that 42 of 85(49%) p53-negative patients were alive, with median survival of 49.9 months, while 8 of 17(47%) p53-positive patients were alive, with median survival of 38.5 months(p=0.28). Survival rates of patients with positive or negative MDM2 staining showed 48 of 89(54%) of MDM2-negative patients were alive, with median survival of 53.0 months, while 3 of 14(21%) MDM2-positive patients were alive, with median survival of 17.7 months (p=0.23). For MDM2, two long-term survivors unduly influenced the results. This is unlikely to be resolved by longer statistical follow-up. HepPar1 diagnostic stain showed that, for negatively stained patients, 11 of 29(38%) were alive, with a median survival of 38.5 months, while for positively stained patients, 39 of 73(53%) were alive, with median survival of 54.3 months(P=0.46). Survival as indicated by prognostic value of HepPar1 stain presented with significant differences. In HepPar1 prognostic stain-negative patients, 12 of 43(28%) were alive, with median survival of 29.5 months, but for patients with positive stain, 38 of 59(64%) were alive, with median survival of 65.4 months(P=0.01). Multivariate analysis of variables, which showed significant differences, served as predictors of mortality; out of these variables, only vascular invasion was a significant predictor of mortality(p=0.05, hazard ratio=2.2).Conclusion: These data suggest differences in survival according to the molecular pathogenesis of HCC based on racial and regional differences. The results to p53, MDM2, and HepPar1 showed a direct correlation between positivity of these proteins and a poorer prognosis for both racial groups. This could explain disparities in clinical outcomes seen for different ethnic cohorts. It also indicates that adjuvant and palliative systemic therapies for general use cannot be directly extrapolated from data derived from one ethnic group.