Abstract: Objective Histone deacetylase 11 (HDAC11) is a class IV member of histone deacetylase family, and its role in regulating cancer cell invasion and metastasis remains unclear. We aimed to investigate the role of HDAC11 in regulating the biological behaviors of basal-like breast cancer (BLBC) cells. Methods We analyzed the expression of HDAC11 based on Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). The effects of HDAC11 on the cell invasion and metastasis were examined using Transwell assay and in a mouse model. The interaction between HDAC11 and Twistwas detected with immunoprecipitation. We identified HAS2 as a target gene of Twist using promoter luciferase assay and chromatin immunoprecipitation assay. Results HDAC11was lowly expressed in BLBC cells.HDAC11 overexpression suppressed BLBC cell invasion in vitro and their metastasis in nude mice. Mechanistically, HDAC11 directly interacted with Twist protein, antagonized its pro-invasive function and repressed Twist-induced HAS2 gene transcription. Conclusion Our data suggest that HDAC11 acts as a negative modulator of invasion and metastasis of BLBC cells.