[Objective]: To explore the thoughts of the addition and subtraction of empirical formula of traditional Chinese medicine. [Methods]: To collect the clinical features of insomnia patients treated by the empirical formula of "si-ni and gui-gan-long-mu" prescription (hereinafter referred as to empirical formula) which contained cocta tuber gingiberi Zhigancao, carina, ostreae and Guizhi" with added and subtracted drugs from professor Zhimin Yang of Guangdong Province Hospital of Traditional Chinese Medical. We use application of association rules (GRI algorithm) to analysis the association rules between the clinical characteristics and addition and subtraction of drugs. [Results]: We collected 40 insomnia patients by the empirical formula of "si-ni and gui-gan-long-mu" with addition and subtraction of drugs from Professor Zhimin Yang, with a total of 106 clinical features. Using association rules (GRI algorithm), respectively analyzing association rules between the 28 drugs of addition and subtraction out of the prescription and 81 clinical characteristics, and we get 12 association rules, including 5 kinds of addition and subtraction drugs which contained white atractylodes rhizome, Poria cocos, Poria cocos with Rhizoma Pinellinae Praeparata, Fresh dogwood with fructus mume, equivalent Guizhi with Aglaophotis radix herbaceu.[Conclusion]: Using the association rules (GRI algorithm), to set the drugs of addition and subtraction as post-item, and the symptoms as pre-item which can meet the clinical characteristic of empirical formula. It is an effective and objective method to explore the empirical formula of addition and subtraction.