To sum up, our studies confirmed that HAND2-AS1 could inhibit BC proliferation, migration, and invasion and induce apoptosis as a ceRNA of miR-3188 to elevate PHLPP2 expression, which poses a potential that HAND2-AS1/miR-3188/PHLPP2 might be a therapeutic axis for breast cancer in the future. This evidence concerns the gene PHLPP2 and breast cancer.