BACKGROUND: Early detection and treatment of hepatocellular carcinoma is crucial to improving the patients' survival. The hemodynamic changes caused by tumors can be serially measured using CT perfusion. In this study, we used a CT perfusion technique to demonstrate the changes of hepatic hemodynamics in early tumor growth, as a proof-of-concept study for human early hepatocellular carcinoma. METHODS: VX2 tumors were implanted in the liver of ten New Zealand rabbits. CT perfusion scans were made I week (early) and 2 weeks (late) after tumor implantation. Ten normal rabbits served as controls. CT perfusion parameters were obtained at the tumor rim, normal tissue surrounding the tumor, and control liver; the parameters were hepatic blood flow, hepatic blood volume, mean transit time, permeability of capillary vessel surface, hepatic arterial index, hepatic arterial perfusion and hepatic portal perfusion. Microvessel density and vascular endothelial growth factor were correlated. RESULTS: At the tumor rim, compared to the controls, hepatic blood flow, hepatic blood volume, permeability of capillary vessel surface, hepatic arterial index, and hepatic arterial perfusion increased, while mean transit time and hepatic portal perfusion decreased on both early and late scans (P<0.05). Hepatic arterial index increased (135%, P<0.05), combined with a sharp increase in hepatic arterial perfusion (182%, P<0.05) and a marked decrease in hepatic portal perfusion (-76%, P<0.05) at 2 weeks rather than at 1 week (P<0.05). Microvessel density and vascular endothelial growth factor showed significant linear correlations with hepatic blood flow, permeability of capillary vessel surface and hepatic arterial index, but not with hepatic blood volume or mean transit time. CONCLUSION: The CT perfusion technique demonstrated early changes of hepatic hemodynamics in this tumor model as proof-of-concept for early hepatocellular carcinoma detection in humans.