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The ARID1Agene, which encodes a subunit of the SWI/SNF chromatin remodeling complex, has been found to be frequently mutated in many human cancer types. However, the function and mechanism of ARID1Ain cancer metastasis are still unclear. Here, we show that knockdown of ARID1Aincreases the ability of breast cancer cells to proliferate, migrate, invade, and metastasize in vivo. The ARID1A-related SWI/SNF complex binds to the second exon of CDH1and negatively modulates the expression of E-cadherin/CDH1by recruiting the transcriptional repressor ZEB2 to the CDH1promoter and excluding the presence of RNA polymerase II. The silencing of CDH1attenuated the migration, invasion, and metastasis of breast cancer cells in which ARID1Awas silenced. ARID1Adepletion increased the intracellular enzymatic processing of E-cadherin and the production of C-terminal fragment 2 (CTF2) of E-cadherin, which stabilized β-catenin by competing for binding to the phosphorylation and degradation complex of β-catenin. The matrix metalloproteinase inhibitor GM6001 inhibited the production of CTF2. In zebrafish and nude mice, ARID1Asilencing or CTF2 overexpression activated β-catenin signaling and promoted migration/invasion and metastasis of cancer cells in vivo. The inhibitors GM6001, BB94, and ICG-001 suppressed the migration and invasion of cancer cells with ARID1A-deficiency. Our findings provide novel insights into the mechanism of ARID1Ametastasis and offer a scientific basis for targeted therapy of ARID1A-deficient cancer cells.