Abstract: In order to accurately calculate the loss of CBM under the effect of drilling fluid, in this paper, with the help of physical chemistry theory, interfacial chemistry theory, surface wetting theory, wetting transition theory, coal chemistry theory and so on, meanwhile through the relevant experiment, the influence of free CBM on loss quantity was discussed. The influence of ''liquid-replaced gas'' and ''water locking'' phenomena on the desorption mechanism of CBM under the effect of drilling fluid was investigated. The results show that CBM desorption of coal core is the result of dynamic coupling of multi-factors under the effect of drilling fluid. CBM in-situ pressure, failure type, granularity, coal rank, core-hoisting velocity and canning time are the main factors influencing the desorption loss of CBM. Furthermore, CBM of coal core have three kinds of desorption process in the medium of drilling fluid and air:displacement desorption, variable pressure desorption, atmospheric pressure desorption.