Abstract: Objective To observe the effect of apolipoprotein E (ApoE) on the invasion and migration ability of colorectal cancer (CRC) cells. Methods The ApoE was over-expressed or silenced by plasmids or siRNAs transfection in CRC cell line SW48, and the expression of ApoE was tested by Real-time-qPCR; then the effect of ApoE on the invasion and migration ability of SW48 cells was detected by Transwell assay; and the effect of ApoE on the expression of matrix metalloproteinase(MMP) family proteins was detected by Western blot. Results RT-PCR test result showed that ApoE mRNA expression in overexpressed ApoE group was significantly higher that those in blank control group and negative control group (P=0.008); there was significant difference in ApoE mRNA expression between silenced ApoE group and negative control group (P=0.013).Transwell invasion assay result showed that cells count in blank control group was (209±17)/field, negative control group (228±11)/field, overexpressed ApoE group (67±9)/field, silenced ApoE (428±15)/field, compared with negative control group (P<0.05); Transwell migration assay result showed that cells count in blank control group was (326±18)/field, negative control group (338±21)/field, overexpressed ApoE group (133±11)/field, silenced ApoE group (518±13)/field, compared with negative control group (P<0.05). Meantime, the overexpression of ApoE could reduce the expression of MMP-2 and MMP-9, and elevate the expression of tissue inhibitors of metalloproteinase-2 (TIMP-2); the silenced ApoE could promote the expression of MMP-2 and MMP-9, and decline the expression of TIMP-2. Conclusion ApoE could regulate the invasion and migration ability of CRC cells, which may be via regulating TIMP-2, MMP-2 and MMP-9 expression.