Does alpha-fetoprotein contribute to the mortality and morbidity of human hepatocellular carcinoma? A commentary Gerald J Mizejewski Wadsworth Center, New York State Department of Health, Albany, NY, USA Abstract: The fifth most common cancer worldwide is hepatocellular carcinoma (HCC), while being the third leading cause of global cancer-related deaths. Although HCC incidence is less frequent in North America, it is a common malignancy in Asia and Africa associated with a high rate of mortality and morbidity due to ineffective therapies against cancer growth, invasion, and metastasis. It is well established that serum alpha-fetoprotein (AFP) is the “gold standard” biomarker for liver cancer; however, less known are the biological activities of AFP regarding carcinogenesis, growth, proliferation, and metastasis. Clinicians are well aware that increasing AFP serum levels parallel disease progression of HCC patients, but many are less knowledgeable in the lethal growth-promoting properties of AFP as an autocrine stimulator of hepatoma cell proliferation. This commentary addresses the mortality and morbidity concerning AFP in the genesis, growth, progression, and spread of HCC and emphasizes the perilous consequences of AFP-supported growth in human liver cancer even after liver resection and transplantation. Thus, AFP is not just a biomarker for HCC but also an ardent promoter of liver cancer growth and progression. Keywords: growth, metastasis, carcinogenesis, proliferation, cancer