The dietary flavonoid quercetin is an antioxidant that possesses antiinflammatory and anticarcinogenic properties and may modulate signaling pathways. Inflammation is considered to play a pivotal role in carcinogenesis by triggering activation of transcription factors such as nuclear factor kappa B (NF-κB), functionally dependent on cellular redox status. This study aims to investigate the antiinflammatory effect of quercetin and its role on the NF-κB pathway, and cyclooxygenase-2 (COX-2) and mitogen-activated protein kinases modulation in a human hepatoma cell line (HepG2). Quercetin alone did not modify any of the parameters analyzed but protected cells against activation of the NF-κB route induced by tumor necrosis factor-α. This inhibitory effect of quercetin was mediated, at least in part, by extracellular regulated kinase, c-jun amino-terminal kinase, and reactive oxygen species, and it was accompanied by reduced COX-2 levels. These observations suggest that quercetin may contribute as an antiinflammatory agent in the liver and provide evidences about its role in the prevention of diseases associated with inflammation, including cancer.