Coalbed methane resource is very abundant in Guizhou Province. In the early stage of exploration and development, there are many drilling difficulties, karst cave were often encountered in the first section drilling with leakage, circulation lost, large dip angle and poor drillability; in the second section drilling, low ROP and thin coal seams led to low core recovery rate, these difficulties seriously restricted the exploration and development process of coalbed methane in Guizhou karst area. By the analysis on the formation characteristics and drilling difficulties of Guizhou karst area and based on years’ engineering practice, this paper summarizes a set of key technologies suitable for coalbed methane drilling in Guizhou karst area, including air drilling technology in the first drilling section, fast drilling technology in the second drilling section and wire-line coring technology. The research results can be suitable not only for the coalbed methane exploration and development in Guizhou karst area, but also can be reference for the coalbed methane exploration and development in other areas.