During the drilling in Block D in Myanmar, the wellbore collapse, the abnormal drill torque and the bit broken falling cuttings were repeatedly encountered, the rate of penetration was reduced, and the drilling progress was seriously affected. This paper focuses on the wellbore instability problems in the process of drilling and developes a drilling fluid system suitable for this block, to improve the drilling speed, reduce the downhole complex accidents. The shale clay composition, the microstructure and the hydration performance of the collapse-prone section in Myanmar block D are analyzed. In view of the existing problems of the early used drilling fluid, the appropriate impermeable and anti-collapse drilling fluid formulation is optimized. The laboratory experiment and evaluation results show that the impermeable and anti-collapse prevention drilling fluids have a strong ability to resist pollution, a good temperature resistance, good clay shale inhibition ability and block ability. In the process of the field application in 4 wells, the drilling fluid shows a good effect on the wellbore stability and can effectively solve the problems of the borehole collapse and the hole enlargement, significantly reduce the downhole complex accidents.