Tumor metastasis leads to a poor prognosis in breast cancer, yet the mechanisms remain unclear. Docosahexaenoic acid (DHA) extracted from Antarctic krill is an optical isomer of common DHA and has a much stronger anti-neoplastic effect. In this work, the migration and invasion abilities of MCF-7 cells treated with low concentrations of Antarctic krill DHA were evaluated. Low concentrations of Antarctic krill DHA significantly reduced the numbers of migrating and invasive MCF-7 cells, whereas the cell numbers decreased slowly in the CD95-silenced MCF-7 cells, which implies that CD95 might be involved in cell migration and invasion. Additionally, co-immunoprecipitation and Western blotting demonstrated that Antarctic krill DHA induced the accumulation of CD95 and caveolin-1 interaction, resulting in the down-regulation of MMP2 expression through the FAK/SRC/PI3K/AKT signaling pathway. In conclusion, Antarctic krill DHA enhanced the interaction between CD95 and caveolin-1, which may led to an inhibitory effect on cell migration and invasion via the FAK/SRC/PI3K/AKT signaling pathway. Our study indicates that Antarctic krill DHA has great potential for tumor therapy and has revealed a new metastatic mechanism mediated by the interaction of CD95 with caveolin-1.