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OBJECTIVE This study aimed to investigate the effect of quercetin on cellular immunity (via IL15 expression) against cancer and to elucidate its regulatory mechanism. MATERIALS AND METHODS HeLa cells and A549 cells were cultured in vitro and were divided into control (DMSO treated) and experimental groups (treated with different concentrations of quercetin). Transcript levels of IL15 and DNA methyltransferase (DNMTS) were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Genomic DNA was extracted, treated with bisulfite, and the promoter region of IL15 was cloned. Finally, Sanger sequencing was used to detect the degree of promoter methylation. RESULTS Following quercetin treatment, the expression of IL15 was significantly downregulated in HeLa and A549 cells. The methylation level of IL15 promoter in HeLa cells was about twice that of the control group, and the methylation level of IL15 promoter in A549 cells was about three times that of the control group. CONCLUSIONS Quercetin inhibits cancer cell proliferation while downregulating IL15 expression, and this regulation is achieved by increasing the methylation of the IL15 promoter.