Macrophage inflammatory protein (MIP-3alpha) is a CC chemokine that attracts immature dendritic cells and lymphocytes and is thought to play a role in the pathogenesis of inflammation and carcinogenesis. However, nothing is known about the clinical significance or prognostic importance of this chemokine in patients with cancer. The aim of this study was to assess the clinical factors influencing the levels of serum MIP-3alpha and to evaluate any possible prognostic importance of this chemokine. We further checked the possible source of MIP-3alpha in hepatocellular carcinoma (HCC). The levels of serum MIP-3alpha from 45 patients with HCC, 12 patients with liver cirrhosis (LC) and 45 patients with chronic hepatitis (CH) were measured by an enzyme immunoassay. A correlationship between different clinical parameters and the serum levels of MIP-3alpha was analyzed. Production of MIP-3alpha by human cancer cell lines and peripheral blood mononuclear cells (PBMC) was also estimated. The levels of serum MIP-3alpha were significantly higher in HCC than in LC (p=0.0214) and CH (p<0.0001). Cancer-related factors such as size of cancer nodules, levels of differentiation of HCC and the levels of alpha-fetoprotein were related with increased MIP-3alpha levels in HCC. Human cancer cell lines, but not PBMC from HCC patients, produced very high levels of MIP-3alpha in culture. The rate of recurrence of HCC after radio frequency ablation (RFA) was fewer in patients having lower pre-therapeutic levels of serum MIP-3alpha. An impact of cancer-related factors on the levels of serum MIP-3alpha in HCC is shown. Pre-therapeutic levels of serum MIP-3alpha may be used as a marker of prognosis of RFA therapy.