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Abstract: Objective: To investigate the influence of Xanthii Fructuson the expression of small non-coding RNAs (snc RNA) and the malignant behaviors of lung cancer cells. Method: A549 human lung cancer cells were cultured and treated with different concentrations (5 -15mg/ml) of the ethanol extract of Xanthii Fructus. The expression of mi R-21and pi RNA55490 was analyzed by Realtime PCR. The proliferation capacity was detected by CCK-8 assay. The anchorage-independent growth capacity was measured by soft agar colony formation experiment. The cell invasion capacity was determined by Matrigel assay. Results: The Xanthii Fructus alcohol extract down-regulated the expression of the oncogenic snc RNAmi R-21, and up-regulated the expression of the tumor suppressive snc RNA pi RNA55490. At the functional level, proliferation, anchorage-independent growth, and invasion capacities of the lung cancer cells were strongly inhibited by the extract treatment. Conclusion: The Chinese herb Xanthii Fructus inhibits the malignant behaviors of lung cancer cells, and the inhibition is largely associated with its ability to change the expression of snc RNAs.