Despite clinical treatments, hepatocellular carcinoma is one of the most common causes of cancer death. We tested whether licofelone, an inhibitor of both cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism, changes the survival rate and induces apoptosis in a hepatoma cell line (H4IIE). We determined in vitro survival rate with MTT assay, the morphological changes with an inverted microscope, apoptosis using flow cytometry and statistical significance with one way analysis of variance followed by Tukey’s multiple comparison test. IC50 values of licofelone were determined as 171 µM for 24 h and 140 µM for 48 h applications. Used as a positive control, 250 µM 5-Fluorouracil decreased the cell survival by only 40 % after 48 h, but licofelone treatment with the same dose and time duration decreased the number of surviving cells by 87 %. Treatments with 150, 200 and 250 µM licofelone caused early apoptotic cell rates of 4, 15 and 24 % for 24 h and 6, 13 and 24 % for 48 h, respectively. In addition, 150, 200 and 250 µM of 5-Fluorouracil resulted early apoptotic cell values of 13, 12, and 11 % for 24 h and 18, 22 and 16 % for 48 h. This study revealed that licofelone possesses dose and time dependent anti-proliferative and apoptotic properties on hepatoma cells.