To extract the total alkaloid of Squilla oratoria and observe its effects on the proliferation and apoptosis of human nasopharyngeal carcinoma line CNE-2Z. Methods Acid extraction and alkaline deposition, and ethyl acetate extraction were used in the extraction and separation of Squilla oratoria, CNE-2Z cells were treated with various concentrations of total alkaloid, then the ability of cell proliferation was detected by CCK-8 assay and colony-forming assay,and the changes of cell cycle distributions were analyzed by flow cytometry. The expression of caspase-8 protein was detected by Western blotting. Results The total alkaloid of Squilla oratoria effectively inhibited the proliferation and colony formation of CNE-2Z cells in certain dose-dependent way, which was related to its induction of cell cycle arrest at S phase. The expression of caspase-8 was decreased after treated with total alkaloid. Conclusion The effect of total alkaloids of Squilla oratoria on CNE-2Z cells can be induced by inhibiting cell proliferation, inducing cell cycle arrest and inducing apoptosis.