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Lycorine is an isoquinoline alkaloid in Amaryllidaceae with antitumor, antibacterial, antiviral, diuretic and cardiovascular effects. This study explored the antitumor mechanism of lycorine in vitro and in vivo by focusing on its effects on tumor cell membrane fraction and tumor cell membrane structure. The results showed that lycorine had antitumor effect on H22 tumor-bearing mice in vivo and could effectively prolong the survival time of H22 tumor-bearing mice. In vitro, lycorine inhibited the proliferation of HepG-2 cells and induced cell death significantly. Lycorine reduced the total protein content, sialic acid content and cholesterol content on the surface of tumor cell membrane, and reduced the content of some main components of tumor cell membranes. Lycorine reduced the membrane fluidity and cell membrane integrity of tumor cells. In addition, the ion channel (Na+, K+-ATPase, Ca2+, Mg2+-ATPase) activity on the surface of the tumor cell membrane decreased. This contributed to a significant antitumor effect in vitro and in vivo. [ABSTRACT FROM AUTHOR]