The invention discloses a method for preparing 2-chlorine-1,1,1,4,4,4-hexafluoro-2-butene by adopting a micro-channel reactor. The method comprises the following steps: (1) activating the catalyst: introducing a liquid fluorination catalyst and anhydrous HF into a micro-channel reactor to obtain an activated catalyst-HF mixture; and (2) carrying out a fluorination reaction: returning the activatedcatalyst-HF mixture prepared in the step (1) into the micro-channel reactor in the step (1), meanwhile, respectively introducing anhydrous HF and hexachlorobutadiene into the micro-channel reactor from a second path and a third path, conveying a mixture obtained after a reaction to a rectifying tower through a pump, extracting a mixture of 2-chlorine-1,1,1,4,4,4-hexafluoro-2-butene and HF from the top of the rectifying tower, and carrying out layering, wherein the lower layer is 2-chlorine-1,1,1,4,4,4-hexafluoro-2-butene, and the upper layer is HF. The method for preparing 2-chlorine-1,1,1,4,4,4-hexafluoro-2-butene has a high conversion rate, high selectivity and few impurities, and activity of the catalyst is greatly prolonged. The silicon carbide micro-channel reactor is adopted, so that the reaction time is short, superacid corrosion resistance is achieved, reaction mass transfer and heat transfer performance is excellent, and therefore, high activity of the catalyst can be kept for a long time.