Caffeic acid (3,4-dihydroxy cinnamic acid) (CA) is naturally found in fruits, vegetables, olive oil, and coffee. This study was undertaken to evaluate the anticancer effect of caffeic acid on HT-1080 human fibrosarcoma cell line. The antiproliferative effect of caffeic acid was determined by MTT assay, and the oxidative stress was determined by lipid peroxidation, changes in the enzymatic, and non-enzymatic antioxidant status. To understand the mode of antiproliferative effect of CA, the authors observed intracellular ROS levels by DCFH-DA method, mitochondrial membrane potential alterations by Rh-123 staining, oxidative DNA damage by comet assay, and apoptotic morphological changes by AO/EtBr-staining method. The results show that caffeic acid enhances lipid peroxidative markers such as TBARS, CD, and LHP in HT-1080 cell line. Caffeic acid enhances the ROS levels, which is evidenced by the increased DCF fluorescence. Further, caffeic acid treatment altered the mitochondrial membrane potential in HT-1080 cells. Similarly, the authors observed increased oxidative DNA damage (% Tail DNA, % Tail length, Tail moment, and olive tail moment), and apoptotic morphological changes in caffeic acid-treated groups. These data suggest that caffeic acid exhibits potent anticancer effect in HT-1080 cell line, and that it may be used as an anticancer agent.