Abstract: Lost circulation control and plugging is the key technology of optimal and fast drilling and cost saving for CBM wells in Guizhou. For karst leakage strata and vicious leakage strata, combining the practice and application of leakage protection and sealing technology in CBM wells, first, attention was paid to well site selection to avoid leakage; Secondly, drilling with DTH hammer and temporary sealing of surface casing can effectively solve the problem of surface leakage; the method of leakage plugging under pressure solves effectively the central malignant leakage problem. This technology improves drilling efficiency, achieves optimal drilling effect, and provides a new way for CBM well drilling in Guizhou to prevent and plug leakage, which has significant application and promotion value.