Genetic toxicity of the refined cuttlefish (Todarodes pacificus) oil (CFO) was assessed through a reverse mutation (RM) test, chromosome aberration (CA) test, and micronucleus (MN) test to confirm the safety of the CFO for a functional ingredient. Five strains (TA98, TA100, TA1535, TA1537, and WP2uvrA) were used for the RM test. In metaphase analysis with and without S9 mix, colonies of all the dosed groups were not increased up to 2 times, compared to that of the negative control. The frequencies of numerical and structural CA by the CFO were not significantly different from those of the negative control. The frequency of micronucleated erythrocyte among polychromatic erythrocytes in all dosed groups was not significantly different from that of the negative control and the CFO did not induce the inhibition of erythrocyte-growth. Also, no dose-dependence was found in every test. In conclusion, the refined CFO had no genetic toxicity because no positive reaction was found through the RM, CA, and MN tests.