Hepatocellular carcinoma (HCC) is one of the most frequent malignancy worldwide. The increasing incidence of HCC in the worldwide has sparked an emerging interest in prognostic markers of HCC. Osteopontin (OPN) is a secreted phosphoprotein which has been associated with progression and metastasis of HCC. Also, peritumoral macrophage (PTM) have been reported to facilitate tumor progression and metastasis. Recently, one study reported that combination of OPN with PTM may predict the prognosis of HCC after curative resection. The authors successfully identified that combination of these two markers is an independent predictor of tumor recurrence and survival in patients with HCC, especially for those with early-stage disease. These findings might support the possibility that combination of OPN and PTM levels can be a prognostic tool. However, further investigations should be conducted before tumor OPN combined with PTMs can be accepted as a valid prognostic marker in clinical practice.