BackgroundThe liver is the third most common metastatic site for advanced breast cancer (BC), and liver metastases predict poor prognoses. However, the characteristic biomarkers of BC liver metastases and the biological role of secreted protein acidic and rich in cysteine-like 1 (SPARCL1) in BC remain unclear. The present study aimed to identify potential biomarkers for liver metastasis of BC and to investigate the effect ofSPARCL1on BC.MethodsThe publicly available GSE124648 dataset was used to identify differentially expressed genes (DEGs) between BC and liver metastases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to annotate these DEGs and understand the biological functions in which they are involved. A protein–protein interaction (PPI) network was constructed to identify metastasis-related hub genes and further validated in a second independent dataset (GSE58708). Clinicopathological correlation of hub gene expression in patients with BC was determined. Gene set enrichment analysis (GSEA) was performed to explore DEG-related signaling pathways.SPARCL1expression in BC tissues and cell lines was verified by RT-qPCR. Furtherin vitroexperiments were performed to investigate the biological functions ofSPARCL1in BC cells.ResultsWe identified 332 liver metastasis-related DEGs from GSE124648 and 30 hub genes, includingSPARCL1, from the PPI network. GO and KEGG enrichment analyses of liver-metastasis-related DEGs revealed several enriched terms associated with the extracellular matrix and pathways in cancer. Clinicopathological correlation analysis ofSPARCL1revealed that its expression in BC was associated with age, TNM stage, estrogen receptor status, progesterone receptor status, histological type, molecular type, and living status of patients. GSEA results suggested that lowSPARCL1expression in BC was related to the cell cycle, DNA replication, oxidative phosphorylation, and homologous recombination. Lower expression levels ofSPARCL1were detected in BC tissues compared to adjacent tissues. Thein vitroexperiments showed thatSPARCL1knockdown significantly increased the proliferation and migration of BC cells, whereas the proliferation and migration were suppressed after elevating the expression ofSPARCL1.ConclusionWe identifiedSPARCL1as a tumor suppressor in BC, which shows potential as a target for BC and liver metastasis therapy and diagnosis.