The present study aimed to identify the association between Epstein-Barr virus (EBV) microRNA (miRNA) and cellular miRNA in compromising the immune system, which contributes to the development of Burkitt lymphoma (BL). The present study selected cellular miR-197 as the focus of the experiments due to the previous report that it is differentially expressed and the observation that interleukin-6 receptor (IL-6R) is a virtual target of miR-197 and EBV-BamHI A region rightward transcript (BART)-6-3p. In the present study, IL-6R was confirmed as a target of cellular miR-197 using a luciferase assay, and the negative regulatory association between miRNA (miR-197 and EBV-BART-6-3p) and mRNA (IL-6R) was confirmed by the observation that IL-6R was downregulated in EBV-positive Burkitt lymphoma and that miR-197 was upregulated. Additionally, mimics of EBV-BART-6-3p and miR-197 were introduced into lymphoma cells, and it was found that EBV-BART-6-3p and miR-197 synergistically reduced the expression of IL-6R. These findings improved current understanding of the role of miR-197/ EBV-BART-6-3p and their target, IL-6R, in the development of EBV-positive BL, and they may offer potential as novel therapeutic targets for the treatment of EBV-positive malignancies.