BACKGROUND This study was designed to explore the molecular mechanism underlying the effect of cellular miRNAs and EBV miRNA upon the expression of targets such as PTEN, and their involvement in the pathogenesis of Burkitt lymphoma. MATERIAL AND METHODS In this study, we examined several differentially expressed cellular miRNAs in EBV-positive versus EBV-negative Burkett lymphoma tissue samples, and confirmed PTEN as targets of cellular miR-142 by using a bioinformatics tool, luciferase reporter system, oligo transfection, real-time PCR, and Western blot analysis. RESULTS We further confirmed the binding site of miR-142 in the 3'UTR of the target genes, and established the negative regulatory relationship between miRNA and mRNAs with luciferase activity assay. To verify the regulatory relationship between the miRNAs and PTEN, we evaluated the expression of PTEN in the tissue samples, and found that PTEN was downregulated in EBV- positive Burkett lymphoma. Additionally, lymphoma cells were transfected with EBV-BART-6-3p and miR-142 and we found that EBV-BART-6-3p and miR-142 synergistically reduced expression of IL-6R and PTEN. Furthermore, we also examined viability of the cells in each treatment group, and showed that EBV-BART-6-3p and miR-142 synergistically promoted proliferation of the cells. CONCLUSIONS These findings improve our knowledge about the role of miR-142/EBV-BART-6-3p and their target, PTEN, in the development of Burkett lymphoma; they could be novel therapeutic targets for the treatment of EBV-positive Burkett lymphoma.