Objective To explore the influences of platelet and platelet-derived 5-hydroxytryptamine (5-HT) on liver function, post-operative recurrence and long-term survival of patients with early stage hepatocellular carcinoma (HCC) following curative resection. Methods Prospective cohort study was employed in this research. A total of 297 consecutive patients who met the Milan criteria and received HCC curative resection from January 2009 to December 2009 in our hospital were selected, and their clinical data were collected. Patients' serum samples were stored at -80℃. Serum 5-HT concentration was detected by ELISA kits. Patients were regularly followed-up to observe their health condition after operation. The influences of PLT and 5-HT on liver dysfunction (LD), overall survival (OS) and recurrence-free survival (RFS) of patients with early stage HCC resection were analyzed via Cox' proportional hazard regression model. Results It was found that the pre- and post-operation PLT counts of patients with post-operation LD were significantly lower than those with normal post-operation liver function (P<0.001). Serum 5-HT concentration was positively correlated with PLT count(r=0.712, P<0.001). Low pre-operative PLT (OR=2.952, 95%CI:1.206-7.229, P=0.018)and low preoperative serum 5-HT concentration (OR=4.989, 95%CI: 2.004-12.422, P=0.001) were the independent risk factors of LD after early stage HCC resection. Low pre-operative PLT (OR=1.782, 95%CI:1.086-2.924, P=0.022) and low pre-operative serum 5-HT concentration (OR=1.754, 95%CI:1.014-3.034, P=0.045) were also the independent risk factors of OS; however, the pre-operative PLT and 5-HT were not the independent risk factors of RFS. Conclusion Early stage HCC patients with low pre-operative 5-HT and PLT tend to have poorer perioperative and long-term outcomes after curative hepatic-resection.