The glycoprotein osteopontin (OPN), which is released by T cells, osteoblasts, and macrophages, is also strongly expressed in various tumors such as Breast, colon, and stomach cancers. Osteopontin acts as an integrin-binding phosphoprotein released at low concentrations by biliary epithelial cells that are overproduced in various kinds of malignancies, involving the lung, breast, and colon. Osteopontin regulates inflammation by interacting with integrin and CD44 receptors OPN tissue expression investigations have revealed that OPN levels are higher in a variety of cancers than in regular tissues. Furthermore, the level of OPN production seems to be linked with the survival of patients and clinicopathological data. OPN, a released protein present in the circulation and in body fluids, has been investigated as a possible noninvasive biomarker for the detection or development of cancer. OPN has a greater sensitivity and specificity than other tumor markers, making it useful for early detection of HCC. Serum OPN levels were significantly raised in severe HCC patients and could be clearly distinguished from non-HCC. According to our research, OPN may be a potential biomarker for HCC, which could make it a useful diagnosis.