Polyunsaturated fatty acids (PUFAs) suppress and induce apoptosis of tumor cells by enhancing free radical generation and accumulation of excess of lipid peroxides. In the present study, we showed that both AA and EPA (AA > EPA) inhibited proliferation of LN229 and HNGC2 (LN229 > HNGC2) cells and suppressed p53, Ras, Myc, BCL-2/Bax, NF-kB/IkB and 5-LOX and enhanced cytochrome C and caspases 3 and 9 expressions and increased the accumulation of lipid peroxides and nitric oxide and altered their antioxidant defenses (LN229 > HNGC2). These studies suggest that accumulation of lipid peroxides seems to be the principle mechanism by which AA and EPA bring about their growth inhibitory action on tumor cells.