AIM: This study was to investigate whether surgery could increase cancer dissemination and postoperative recurrence in patients with hepatocellular carcinoma (HCC) by detection of human α-fetoprotein messenger RNA (hAFP mRNA), hAFP mRNA in the peripheral blood of patients with HCC has been considered as a surrogate marker for circulating tumor cells.METHODS: Eighty-one consecutive patients who underwent curative resection for HCC entered this prospective cohort study. We examined hAFP mRNA from the peripheral blood obtained preoperatively, perioperatively, and postoperatively to correlate the prognosis after curative resections from HCC patients and from the control subjects. Detection of hAFP mRNA by reverse transcriptase and polymerase chain reaction amplification (RT-PCR) was performed with primers specifically. The relations between the clinical variables (age,sex, associated liver cirrhosis, hepatitis B virus infection,hepatitis C virus infection, serum α-fetoprotein and ChildPugh class), the histological variables (size, capsule, vascular permeation, grade of differentiation, and daughter nodules),hAFP mRNA in peripheral blood of 3 different sessions, and postoperative course (recurrence, and recurrence related death) were analysed.RESULTS: No hAFP mRNA was detected in control group subjects. Twenty-two (27%), 24 (30%) and 19 (23%) of 81 HCC patients had hAFP mRNA positivity in the preoperative,perioperative and postoperative peripheral blood. The preoperative presence did not influence the risk of HCC recurrence (55% vs41%, P=0.280). In contrast, patients with postoperative presence had a significantly higher recurrence (90% vs 31%, P＜0.001; odds ratio 19.2; 95% confidence interval: 4.0-91.7). In the multivariate analysis by COX proportional hazards model, postoperative positivity had a significant influence on recurrence (P=0.067) and recurrence related mortality (P=0.017). Whereas, the perioperative positivity of hAFP mRNA did not increase HCC recurrence (58% vs.39%, P=0.093). The correlation between perioperative hAFP mRNA positivity and recurrence related mortality had no statistical significance (P=0.836).CONCLUSION: From our study, perioperative detection of hAFP mRNA in peripheral blood of patients has no clinical relevance and significant role in the prediction of HCC recurrence. Surgical resection itself may not accelerate cancer dissemination and does not increase postoperative recurrence significantly either.