RTN4IP1 interacts with a membranous protein of endoplasmic reticulum (RTN4), this study was to explore the role RTN4IP1 involved in breast cancer (BC). After RNAseq data of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) project were downloaded, correlations between RTN4IP1 expression and clinicopathologic variables, as well as expression levels between cancerous samples and non-cancerous ones were tested. Differentially expressed genes (DEGs) and functional enrichment, gene set enrichment analysis (GSEA) and immune infiltration analysis were conduct for bioinformatics analysis. After logistic regression, Kaplan-Meier curve of disease-specific survival (DSS), univariate and multivariate COX analysis, a nomogram was established for prognosis. RTN4IP1 expression was up-regulated in BC tissue, significantly associated with estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status (P<0.001). The 771 DEGs linked RTN4IP1 to glutamine metabolism and mitoribosome-associated quality control. Functional enrichment pointed to DNA metabolic process, mitochondrial matrix and inner membrane, ATPase activity, cell cycle and cellular senescence; whereas GSEA indicated regulation of cellular cycle, G1_S DNA damage checkpoints, drug resistance and metastasis. Eosinophil cells, natural killer (NK) cells and Th 2 cells were found to be correlated with RTN4IP1 expression (R=-0.290, -0.277 and 0.266, respectively, P<0.001). RTN4IP1high BC had worse DSS than RTN4IP1low ones [hazard ratio (HR) =2.37, 95% confidential interval (CI): (1.48-3.78), P<0.001], which has independent prognostic value (P<0.05). Overexpressed in BC tissue, RTN4IP1 predicts adverse prognosis for patients with BC, especially in infiltrating ductal carcinoma, infiltrating lobular carcinoma, Stage II, Stages III&IV and luminal A subtype.