The invention discloses a tetrodotoxin pharmaceutical composition for treating pain diseases. The tetrodotoxin pharmaceutical composition contains 1 to 1000mu g/unit dose of tetrodotoxin and/or a derivative of the tetrodotoxin and further is prepared from the following bulk drugs in weight: radix notoginseng, semen vaccariae, fructus anisi stellati, fructus foeniculi, radix angelicae dahuricae, rhizoma bletillae, pericarpium zanthoxyli, rhizoma chuanxiong, herba speranskiae tuberculatae, cortex acanthopanacis, origanum vulgare herb, flos cartham, rhizoma gastrodiae, borneol, musk and herba taraxaci. The invention further discloses a preparation method of the tetrodotoxin pharmaceutical composition for treating the pain diseases. The invention further discloses an externally-used medicine prepared from the tetrodotoxin pharmaceutical composition for treating the pain diseases. The externally-used medicine of the tetrodotoxin pharmaceutical composition disclosed by the invention has convenient and simple use method, avoids special instruments or devices, has no technical requirement, has controllable untoward effect and very wide adaptation diseases, is not only limited to treat various acute and chronic pain, but also has reliable analgesic effect and further can be applied to treating various of non-pain symptoms and diseases.