Clinical and epidemiological studies show that docosahexaenoic acid (DHA) and arachidonic acid (AA) exert multiple effects on ovarian cancer. While DHA seems to inhibit growth and prevent carcinogenic processes, stimulation of leukotriene B4 receptors BLT1 and BLT2 by several eicosanoids derived from AA plays an important role in mediating cisplatin resistance in ovarian cancer cells. We examined whether DHA and AA exerted antiproliferative effect on epithelial ovarian cancer cells and whether these polyunsaturated fatty acids could alter their susceptibility to cisplatin. Using SKOV3 and OVCAR3 cell lines, we found that DHA but not AA suppressed the cells viability, proliferation, enhanced cell death, and induced activation of caspase-3/7 in the concentration- and time-dependent manner. The OVCAR3 cells were less susceptible to cisplatin than SKOV3 cells. DHA but not AA significantly potentiated cisplatin cytotoxicity in SKOV3 and OVCAR3 cells. We did not observe any significant influence of AA on the above mentioned processes in both cell lines. Similar effect can occur in ovarian cancer patients treated with cisplatin and supplemented with DHA.