CXCR5 is a chemokine receptor that promotes B cell follicular formation and antibody production. Indeed, CXCR5 has been found to be expressed in a variety of cancers; however, the role of CXCR5 expression in clear-cell renal cell carcinoma (ccRCC) remains unclear. We aimed to determine the impact of cellular CXCR5 expression on cancer outcomes, the PD-1/PD-L1 axis, and genetic states in patients with ccRCC. First, multiplex immunofluorescence staining for CXCR5, CD4, CD8, and AE1/AE3, along with automated single-cell counting, was performed to assess cellular CXCR5 expression in ccRCC and its association with prognosis. Second, the tumour microenvironment (TME) was analysed, with a focus on the relationship between the PD-1/PD-L1 axis and CXCR5 expression. Finally, an integrated analysis of CXCR5 expression and genomic mutation information was conducted to reveal the genetic background underlying CXCR5 expression. A total of 105 ccRCC patients were included. Among the 696,964 cells analysed, the distribution of CXCR5-expressing cells was as follows: 30% CXCR5CD4 cells, 9% CXCR5CD8 cells, and 26% CXCR5AE1/AE3 cells. Survival analysis revealed that tumours with low-CXCR5CD8 cells had a poor prognosis; TME analysis revealed a relationship between low-CXCR5CD8 status and a highly suppressive PD-L1-positive immune environment. Genomic analysis revealed a correlation between low-CXCR5CD8 status and high rates of alterations in chromatin remodelling genes, including PBRM1. This study highlights the significance of CXCR5CD8 cells in ccRCC, demonstrating their clinical implications and revealing the immunogenomic landscape underlying CXCR5 expression.