AIM: To investigate the prognostic role of isoform 165 vascular endothelial growth factor messenger RNA (VEGF165 mRNA)in noncancerous liver tissues from patients with primary hepatocellular carcinoma (HCC).METHODS: Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, VEGF mRNA was determined prospectively in noncancerous liver tissues from 60 consecutive patients with HCC undergoing curative resection. We categorized the patients with VEGF165 mRNA over 0.500 in noncancerous liver tissues as group A, and those below 0.500 as group B.RESULTS: Among the isoforms of VEGF mRNA by multivariate analysis, a higher level of VEGF165 mRNA in noncancerous liver tissue correlated significantly with a higher risk of HCC recurrence (P = 0.039) and recurrence-related mortality (P= 0.048), but VEGF121 did not. The other significant predictors of recurrence consisted of vascular permeation (P = 0.022),daughter nodules (P = 0.033), cellular dedifferentiation (P = 0.033), an absent or incomplete capsule (P = 0.037).A significant variable of recurrence-related mortality was Vascular permeation (P= 0.012). As to the clinical manifestations of 16 patients who developed recurrence,the recurrent tumor number over 2, recurrent extent over two-liver segments, and the median survival after recurrence,all significantly correlated with group A patients (P = 0.043,0.043, and 0.048, respectively). However, the presence of extrahepatic metastasis was not (P＞0.05). The difference in recurrence after treatment between the two groups had no statistical significance (P＞0.05).CONCLUSION: The higher expression of isoform VEGF165mRNA in noncancerous liver remnant of patients with HCC may be a significant biological indicator of the invasiveness of postoperative recurrence.