Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) is known to be a useful marker for the diagnosis of hepatocellular carcinoma (HCC). Recent studies have shown that positive AFP-L3 results after treatment predicts tumor recurrence and poor clinical outcome. This study was to evaluate the role of pretreatment AFP-L3 as a prognostic marker for response to transcatheter arterial chemoembolization (TACE) and survival in patients with HCC. Forty-six patients with HCC who underwent TACE were analyzed. Agglutinin-reactive AFP was measured by lectin-affinity electrophoresis coupled with antibody-affinity blotting. Agglutinin-reactive AFP results larger than 24.4% were considered to be positive. Agglutinin-reactive AFP fractions were positive in 32 patients. Agglutinin-reactive AFP-positive patients had poorer performance status, larger tumors, frequent portal vein thrombosis, and higher levels of serum AFP. The partial response rate to TACE was lower in AFP-L3-positive patients than in AFP-L3-negative ones (37.5% vs. 78.6%, p = 0.01). Tumor size and AFP-L3 were two independent predictive factors for response to TACE. The 2-year survival rate was lower in AFP-L3-positive patients than in AFP-L3-negative ones (21.2% vs. 78.6%, p = 0.01). Child-Pugh class, AFP-L3, the presence of portal vein thrombosis, and response to TACE were independent prognostic factors for survival. In conclusion, pretreatment status of AFP-L3 could be considered a useful marker for predicting clinical outcome in patients with HCC who underwent TACE.