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MiRNA16 is known to abnormally expressed in liver cancer hepatocellular carcinoma (HCC). Overexpression of miRNA-16 inhibits proliferation, invasion, and metastasis of various cancer cells including live cancer. Monitoring the progress and success of cancer treatment has been high cost. Another consideration is with biomarkers taken from the blood that is minimally invasive. Detection of miRNA levels has potency for the initial diagnosis of malignancy, prognosis prediction and can monitored the therapeutic response because miRNA is very stable in the blood. It was hypothesized that flavonoid from clove leaf oil will be able to interfering MiRNA-16 expression. This study was used the HepG2 cell line culture and treatment groups were given active compound isolated from clove leaf oil. Measurement of gene expression was done with real-time PCR. In this study, the measurement of miRNA-16 expression in liver cancer cell culture after administration of flavonoid pure compounds from clove leaf oil showed an increase in expression almost 24 times the level of expression of the control group. The study conclude that flavonoid compound from clove leaf oil can interfered miRNA-16 expression on liver cancer cells culture.