Treacle ribosome biogenesis factor 1 (TCOF1) plays a crucial role in multiple processes, including ribosome biogenesis, DNA damage response (DDR), mitotic regulation, and telomere integrity. However, its role in cancers remains unclear. We aimed to visualize the expression, prognostic, and mutational landscapes of TCOF1 across cancers and to explore its association with immune infiltration. In this work, we integrated information from TCGA and GEO to explore the differential expression and prognostic value of TCOF1. Then, the mutational profiles of TCOF1 in cancers were investigated. We further determined the correlation between TCOF1 and immune cell infiltration levels. Additionally, we determined correlations among certain immune checkpoints, microsatellite instability, tumor mutational burden (TMB), and TCOF1. Potential pathways of TCOF1 in tumorigenesis were analyzed as well. In general, tumor tissue had a higher expression level of TCOF1 than normal tissue. The prognostic value of TCOF1 was multifaceted, depending on type of cancer. TCOF1 was correlated with tumor purity, CD8+ T cells, CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells (DCs) in 6, 14, 16, 12, 20, 13, and 17 cancer types, respectively. TCOF1 might act on ATPase activity, microtubule binding, tubulin binding, and catalytic activity (on DNA), and participate in tumorigenesis through “cell cycle” and “cellular-senescence” pathways. TCOF1 could affect pan-cancer prognosis and was correlated with immune cell infiltration. “Cell cycle” and “cellular-senescence” pathways were involved in the functional mechanisms of TCOF1, a finding that awaits further experimental validation.