Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is associated with poor clinical prognosis and high mortality, despite the advances related to therapeutic options for HCC. Therefore, exploring alternative therapeutic options and their associated mechanisms is relevant and urgently needed. Natural products may be an important source of novel anti-cancer compounds. Coffee consumption is associated with protective effects against liver diseases, but the molecular mechanisms underlying these benefits remain poorly understood. Objectives: In this study, we evaluated the in vitro effects of green (GC) and roasted coffee (RC) extracts, alongside chlorogenic acid (CGA), on the proliferation of HepG2 hepatocellular carcinoma cells.