Cancer is a prevalent and dangerous disease that requires a multifaceted approach to treatment. The FCRL family gene has been linked to immune function and tumor progression. Bioinformatics may help unravel their role in cancer treatment. We conducted a comprehensive analysis of the FCRL family genes in pan-cancer using publicly available databases and online tools. Specifically, we examined gene expression, prognostic significance, mutation profiles, drug resistance, as well as biological and immunomodulatory roles. Our data were sourced from The Cancer Genome Atlas, Genotype-Tissue Expression, cBioPortal, STRING, GSCALite, Cytoscape, and R software. The expression of FCRL genes varies significantly across different tumor types and normal tissues. While high expression of most FCRL genes is associated with a protective effect in many cancers, FCRLB appears to be a risk factor in several types of cancer. Alterations in FCRL family genes, particularly through amplification and mutation, are common in cancers. These genes are closely linked to classical cancer pathways such as apoptosis, epithelial-mesenchymal transition (EMT), estrogen receptor (ER) signaling, and DNA damage response. Enrichment analysis indicates that FCRL family genes are predominantly associated with immune cell activation and differentiation. Immunological assays demonstrate a strong positive correlation between FCRL family genes and tumor-infiltrating lymphocytes (TILs), immunostimulators, and immunoinhibitors. Furthermore, FCRL family genes can enhance the sensitivity of various anticancer drugs. The FCRL family genes are vital in cancer pathogenesis and progression. Targeting these genes in conjunction with immunotherapy could enhance cancer treatment efficacy. Further research is required to determine their potential as therapeutic targets.