Background: There are 13283 people per 100 000 were diagnosed with skin cancer in 2016. Skin cancer is reported not widely in Mongolia. However, melanoma and non-melanoma new case are gradually increasing since 2010. Rhubarb is an old and well-known traditional Mongolian herbal medicine. Rhubarb is rich of bioactive compounds and widely distributed around Mongolia. People are still using Rhubarb as in food consumption and traditional medical treatments. Yet, there is not reported any therapeutic effect of rhubarb based on scientific research.PurposeTo investigate the anti-cancer activities of rhubarb (Rheum undulatum.L), a new herbal preparation from Mongolia, on B16F10 cells Material and Methods: The shoot of rhubarb was soaked with 40% ethanol and methanol. Murine melanoma B16F10 and RAW264.7 macrophage cell lines were purchased from the American Type Culture Collection (ATCC). Cell viability was determined CCK-8 assay. The antimigratory effect of Rhubarb (50-400 μg/μl) was investigated by a wound healing assay for 12 hours. Apoptosis was then evaluated by Western blot analysis. All experiments conducted at Core laboratory of Mongolian national university of medical sciences and Genomics laboratory of Mongolian university of life sciences from November 2015 to February 2017. Results: Ethanol and methanol extract of rhubarb inhibited the proliferation of B16F10 and RAW264.7 cells. In WHMA, cell migration was gradually decreased by concentrate dependent groups compare to the control group. Furthermore, protein expression PARP, Akt, BCL2, BAX and mTOR was investigated. BAX, Akt were down-regulated by rhubarb extraction as expected. DNA fragmentation assay have shown a dose dependent increase in the fragmentation of the DNA signifying apoptotic changes in the R.u extract treated B16F10 cells. Conclusion Rhubarb (Rheum undulatum.L) shows promising anti-cancer activity and can be useful in therapeutic treatment of skin cancer.