BACKGROUND: The study aimed to explore the clinical value of mitochondrial ribosomal protein L18 (MRPL18) in breast cancer. METHODS: Multiple databases were used to validate the expression of MRPL18. The prognostic impact and predictive value of MRPL18 were evaluated by using predictive models. Protein-protein interaction (PPI) networks were constructed by using GeneMANIA. Enrichment analysis is used to explore the signaling pathway regulated by MRPL18. Cell counting kit-8 (CCK-8) assays, colony formation, migration assays, flow cytometry, and xenograft models were employed to evaluate the role of MRPL18 in tumor progression. The immune response of MRPL18 was examined using correlation analysis. RESULTS: High levels of MRPL18 are considered a risk factor in breast cancer. In vitro and in vivo studies demonstrated that MRPL18 promotes proliferation and migration in breast cancer. Besides, results found that MRPL18 promotes tumor growth through the activation of phosphatidylinositol 3-kinase (PI3K). Furthermore, high MRPL18 expression was linked to reduced immunotherapy efficacy, as indicated by correlations with immune checkpoints and immune-infiltrating patterns. CONCLUSION: MRPL18 promotes the progression of breast cancer.