Aim: Transforming growth factor (TGF) is overexpressed by tumor cells like other proteins and growth factors. TGF-β1 is then activated in the extracellular compartment but is unable to control cell proliferation because of the absence or low level of TGF-β1 receptors on the plasma membrane of malignant hepatocytes. This potential mechanism might interrupt the autocrine regulation loop of TGF-β1 and its blocking effect on cell proliferation. TGF-β1 is a multifunctional cytokine involved in the regulation of growth and differentiation of both normal and transformed cells. This study aimed to evaluate the association of serum levels of TGF-β1 with disease severity. Methods: A total of 180 subjects were classified into 6 groups according to Barcelona clinic liver cancer (BCLC) classification, 30 patients each: early (BCLC 0 and A), intermediate (BCLC B), advanced stage (BCLC C), and terminal stage (BCLC D) of hepatocellular carcinoma as well as 1 group of patients with cirrhosis only and 1 control group. Serum levels of TGF β1 were measured. Results: Serum levels of TGF-β1 were significantly higher in patients with HCC (1,687.47 ± 1,462.81 pg/mL) than cirrhotics (487.98 ± 344.23 pg/mL, P < 0.001) and controls (250.16 ± 284.61 pg/mL, P < 0.001). Conclusion: TGF-β1 may have a role in tumor growth and progression.