Breast cancer is the most common malignancy in females and poses a significant health threat to women. Pregnancy-associated plasma protein-A (PAPPA) is highly expressed in pregnancy-associated breast cancer (PABC) tissues. In this study, we investigated the functional role of PAPPA in regulating the malignant phenotype of breast cancer. We first examined the expression level of PAPPA in PABC tissue and breast cancer cell lines using quantitative real-time polymerase-chain reaction (qRT-PCR) and western blot. Next, the functional role of PAPPA in breast cancer cells was validated by overexpression and knockdown experiments. Cell counting kit-8 (CCK-8) proliferation assay, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, wound healing and transwell invasion assay were used to examine cell proliferation, migration, and invasion ability. We further identified the microRNA target regulating PAPPA and studied its functional role. Finally, we examined the impact of PAPPA on the tumorigenesis and metastasis of breast cancer in mice model. Our study revealed that PAPPA was upregulated in PABC tissues and breast cancer cells. Overexpression of PAPPA promoted cell proliferation, motility, invasion, and epithelial-mesenchymal transition (EMT). We further identified miR-497-5p as a negative regulator of PAPPA, which suppressed cell proliferation, migration, invasion, and EMT in breast cancer cells. We also validated the oncogenic role of PAPPA in the mouse xenograft model. Collectively, our study suggests that PAPPA is an oncogenic protein highly expressed in PABC tissues and promotes breast cancer progression, which could serve as a novel therapeutic target for breast cancer.