Here, we: (i) summarize current knowledge on IL-8’s role in tumor–stroma interactions (TSI); (ii) analyze IL-8 expression in CRC; and (iii) discuss the results of an updated meta-analysis of published studies focusing on the relationship between IL-8 expression levels and outcomes (overall survival [OS] and progression-free survival [PFS]) in advanced CRC. This evidence concerns the gene CXCL8 and neoplasm.