Background: Breast cancer is the most common cancer among women and the second most common cancer among newly diagnosed cancers worldwide. At present, long non-coding RNAs (lncRNAs) are widely reported to be involved in the occurrence and development of multiple cancers. As a newly discovered long non-coding RNA, the function of HLA complex group 11 (HCG11) remain uncertain in breast cancer. This article aims to examine the effect of HCG11 in breast cancer.Methods: RT-PCR was performed to detect the mRNA level of HCG11 in both breast cancer tissues and cell lines. HCG11 overexpression virus and siHCG11 were constructed and transfected to the breast cancer cell line MCF-7. The effect of HCG11 were evaluated by CCK-8 assay, colony formation assay, wound scratch assay, and cell invasion assay. Then we found and determined small RNA that may interact with HCG11 by bioinformatics analysis and luciferase report analysis. Next, we further researched the role of miR-330-3p in HCG11-mediated breast cancer by CCK-8 assay, colony formation assay, wound scratch assay, and cell invasion assay. At last, the above experimental methods and nude mouse experiments were used to confirm the role of HCG11/miR-330-3p/ FOXO1 in breast cancer process.Results: The results showed that the mRNA level of HCG11 was low-expressed in breast cancer tissues and cell lines. HCG11 overexpression inhibited cell proliferation, invasion and migration in MCF-7 cell line. Moreover, HCG11 could target miR-330-3p/FOXO1 and further suppressed the progression of breast cancer. Conclusion: In summary, lncRNA HCG11 suppressed the progression of breast cancer through cooperating with miR-330-3p/FOXO1 axis