Herein, we established the fingerprint of Ligusticum chuanxiong, and the effects of different ⁶⁰Co-γ irradiation doses on the eight active components of Ligusticum chuanxiong were investigated. A stock solution of the eight standard reference substances in Ligusticum chuanxiong were analyzed using a SHIMADZU Shim-pack GIST C18 chromatographic column (250 mm × 4.6 mm, 5 μm). Different doses (3 kGy, 6 kGy,10 kGy and 15 kGy) of ⁶⁰Co-γ irradiation were used to treat Ligusticum chuanxiong. After these treatments, the fingerprint of Ligusticum chuanxiong was obtained via liquid chromatography. The similarity was evaluated using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (2004 A edition), and the results indicated that the similarity of each component in Ligusticum chuanxiong was >0.988. After irradiation at <10 kGy, the contents of the eight active components in Ligusticum chuanxiong exhibited no evident differences, and the results indicated the stability and reliability of the method. Thus, this study provides a theoretical basis and support for the use of irradiation technology in the quality assurance of Ligusticum chuanxiong and the formulation of irradiation standards for Ligusticum chuanxiong.