Abstract：Objective：To investigate the antitumor effect and possible mechanism of pomegranate peel polyphenols in lung cancer. Methods： The expression level of miR- 4316 in lung cancer tissues was detected by RT- qPCR. Lung cancer cells A549 were divided into pomegranate peel polyphenols- low group ， pomegranate peel polyphenols-medium group ， pomegranate peel polyphenols-high group ， control group， miR- NC group， miR- 4316 group， pomegranate peel polyphenols + anti- miR- NC group and pomegranate peel polyphenols+anti-miR- 4316 group. Cell migration，proliferation and invasion were detected by scratch healing assay，plate cloning assay，CCK-8 assay and Transwell assay，respectively. Results： The expression level of miR- 4316 in lung cancer tissues was significantly decreased (P＜0.05). The inhibition rate of A549 cells and the level of miR- 4316 in pomegranate peel polyphenols (- low， - medium and - high) groups were higher than those in control group，and the number of clone formation， scratch healing rate and invasion number were lower than those in control group (P＜0.05). Compared with the miR- NC group，the inhibition rate of A549 cells in the miR- 4316 group was significantly higher than that in the miR-NC group (P＜0.05)，and the number of clone formation，scratch healing rate and invasion number in the miR-4316 group were lower than that in the miR-NC group (P＜0.05). The inhibition rate of A549 cells in pomegranate peel polyphenols + anti- miR- 4316 group was lower than that in pomegranate peel polyphenols +anti-miR-NC group (P＜0.05). The number of clone formation，scratch healing rate and invasion number of pomegranate peel polyphenols + anti- miR- 4316 group were higher than those of pomegranate peel polyphenols +anti-miR-NC group (P＜0.05). Conclusion：Pomegranate peel polyphenols inhibit the proliferation，migration and invasion of lung cancer cells by up-regulating the expression of miR- 4316.