Ellagic acid (EA) is a natural dietary polyphenol whose benefits in a variety of diseases shown in epidemiological and experimental studies involve anti-inflammation, anti-proliferation, anti-angiogenesis, anti-carcinogenesis and anti-oxidation properties. This study aimed to evaluate the effect of EA against paraquat (PQ)-induced oxidative stress. PQ decreased the viability of A549 cells in dose- and time-dependent manners, which was associated with the massive generation of reactive oxygen species (ROS). However, cell viability was significantly recovered by the treatment of EA, from 47.01±1.59% to 66.04±2.84%. The release of lactate dehydrogenase (LDH) was also decreased with the treatment of EA in PQ-treated A549 cells. EA induced the level of expression and activation of nuclear factor-erythroid 2-related factor (Nrf2) and its target cytoprotective and antioxidant genes, heme oxygenase-1 ( HO-1 ) and quinone oxidoreductase 1 ( NQO1 ). The antioxidant potential of EA might be directly correlated with the increased expression of HO-1 and NQO1, whose expression may have surmounted the oxidative stress generated by PQ. Notably, EA treatment significantly reduced the levels of biochemical markers as lipid peroxidation, reduced the intracellular ROS level, and surmounted total glutathione level in A549 cells. Data indicate that the antioxidant and cytoprotective properties of EA reduce PQ-induced cytotoxicity in human alveolar A549 cells.