Objective To investigate the rules of medication and combinations of anti-tumor formulas containing marine Chinese medicinals. Methods The anti-tumor formulas containing marine Chinese medicinal were collected from Marine Chinese Medicinal and Effective formulas, Dictionary of Chinese Marine Medicinals, Marine Chinese Materia Medica, and databases including CNKI. A database was established for data mining by using V2. 5 software of TCM inheritance support system (TCMISS). Results There were totally 251 anti-tumor formulas containing marine Chinese medicinals involved 417 Chinese medicinal including 36 marine Chinese medicinals. The nature of medicinals in these formulas were mainly cold, neutral and warm, flavors of them were mainly bitterness, pungency, sweetness and saltiness,and they mainly entered into meridians of liver,lung,stomach,spleen and heart. The analysis of association rules showed that core combination was Muli (Oyster Shell, Concha Ostreae)-Haizao (Seaweed, Sargassum)-Kunbu (Kelp, Thallus Laminariae), which was commonly combined with medicinals with effects of clearing heart,tonifying,resolving phlegm,dissipating binds,activating blood and resolving stasis in clinical practice. Entropy clustering analysis showed that there were 12 combinations with core medicinals,and they were Haizao-Haigeqiao(Clam Shell,Goncha Meretricis seu Cyclinae)-Kunbu, Zaojiaoci (Chinese Honeylocust Spine, Spina Gleditsiae)-Chuanshanjia (Pangolin Scales,Squama Manitis)-Jiangcan (Batryticated Silkworm, Bombyx Batryticatus), Muxiang (Common Aucklandia Root,Radix Aucklandiae)-Walengzi (Ark Shell, Concha Arcae)-Puhuang (Cattail Pollen, Pollen Typhae), Chansu (Toad Venom, Venenum Bufonis)-Xionghuang (Realgar, Realgar)-Zhenzhu (Pearl,Pernulo),Huangbai(Amur Cork-Tree,Cortex Phellodendri)-Yunaoshi(Fish Otolith,Asteriscus Pseudosciaenae)-Bingpian (Bomeol, Bomeolum Syntheticum), Haima (Sea Horse, Hippocampus)-Qingpi (Green Tangerine Peel, Pericarpium Citri Reticulatae Viride)-Qianniuzi (Pharbitis Seed, Semen Pharbitidis), Haizao-Kunbu-Gancao (Liquorice Root, Radix Glycyrrhizae), Wangbuliuxing (Vaccaria Seed,Semen Vaccariae)-Chuanshanjia-Muli, Fengfang (Hornet Nest, Nidus Vespae)-Walengzi-Qianxie (Scorpion,Scorpio),Shexiang (Musk,Moschus)-Xuejie (Dragon's Blood,Risina Draconis)-Zhenzhu, Huangbai (Amur Cork-Tree, Cortex Phellodendri)-Ruxiang (Frankincense, Olibanum)-Bingpian, and Qingpi-Wulingzhi (Trogopterus Dung, Faeces Trogopterorum)-Dafupi (Shell of Arecanut, Pericarpium Arecae). There were 6 new combinations, and they were Haizao-Haigeqiao-Kunbu-Gancao, Zaojiaoci-Chuanshanjia-Jiangcan-Wangbuliuxing-Muli, Muxiang-Walengzi-Puhuang-Fengfang-Qianxie, Chansu-Xionghuang-Zhenzhu-Shexiang-Xuejie, Huangbai-Yunaoshi-Bingpian-Ruxiang, and Haima-Qingpi-Qianniuzi-Wulingzhi-Dafupi. The high-frequency tumor diseases, totally 47, treated with anti-tumor for-mulas containing marine Chinese medicinals,were successively thyroid tumor,lung cancer,liver cancer, uterine fibroids, nasopharyngeal carcinoma, esophageal cancer, gastric cancer and mammary cancer. Conclusion There are rules to follow in treatment of tumors with marine Chinese medicinal. The different therapeutic effects can be achieved by different medicinal combinations,which has a very important value in guiding clinical medication and new medicinal development.