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Neuroblastoma breakpoint family, member 1 (NBPF1), appears to be a double-edged sword with regard to its role in carcinogenesis. On the one hand, the tumor-suppressing functions of NBPF1 have been definitively observed in neuroblastoma, prostate cancer, cutaneous squamous cell carcinoma, and cervical cancer. On the other hand, there is evidence that NBPF1 regulates the colony formation, invasion, and maintenance of liver cancer cells and hence functions as an oncogene. The roles of NBPF1 are strictly dependent on the biological context and type of organization. However, a systematic pan-cancer analysis has thus far not been undertaken, and the significance of NBPF1 in the occurrence and progression of many malignancies is uncertain. In this paper, bioinformatics techniques were employed to analyze NBPF1 expression across different cancers and investigate the relationship between NBPF1 and clinical features, prognosis, genetic alteration, and tumor immune microenvironment, respectively. Our results show that NBPF1 is variably expressed in distinct tumor tissues and is also closely linked to clinical outcomes. In particular, compared to other tumor types, there was a strong negative correlation between NBPF1 expression and various components of the tumor microenvironment in adrenocortical carcinoma (ACC). We thus developed an NBPF1-derived immune risk model based on NBPF1-related immune genes; ACC patients with a high-risk score tended to have a poorer prognosis, accompanied by immune hyporesponsiveness. NBPF1 can be used as a prognostic biomarker for multiple cancers. Moreover, anti-NBPF1 immunotherapy may be suitable for treating ACC patients.