Abstract: Well LS25-1S-1 is a deep water HTHP well drilled to 4 448 m, completed at the Meishan Formation. A six-interval well profile was adopted during drilling. The predicted pressure coefficient of the φ212.7 mm target section was 1.70-1.84. Narrow safe drilling window, blowout, lost circulation and the formation of gas hydrate were all problems that needed to be addressed. Meanwhile, the bottom hole temperature and the wellhead temperature are 147℃ and 17℃, respectively, requiring the high density drilling fluid to have good high temperature and low temperature stability, good performance in preventing barite settlement, and good rheology. Gas samples from the block LS were used in studying the formation of gas hydrate. HydraFLASH, a computer software, was used to draw the P-T phase diagram of gas hydrates at different concentrations of gas hydrate inhibitors. From the P-T phase diagram, a gas hydrate inhibition formulation used during drilling and non-drilling processes was formulated:(9%-15%) NaCl+5%KCl+10% KCOOH+ (0-45%) MEG. A high temperature filter loss reducer, HTFL was selected to control fluid loss. At a concentration of 0.8% HTFL, the HTHP filter loss of the formulated drilling fluid was less than 10 mL, and quality of the mud cake was satisfactory. PF-FPA, a newly developed plugging agent, was used in the drilling fluid, and it had better plugging performance than another plugging agent FLC2000. In laboratory evaluation, the drilling fluid formulated showed high temperature stability (170℃), stable rheology at both high temperature and low temperature, resistance to 10% calcium bentonite contamination, good settlement stability and plugging performance, and recovery of permeability higher than 80%. In filed application, through simulation with computer software Drill Bench, the flow rate was reduced to 1 400 L/min, and the corresponding ECD was 1.94 g/cm³, lower than the equivalent density of 1.96 g/cm³, at which lost circulation would occur. At ROP of 10 m/h, the efficiency of carrying drill cuttings out of hole was still higher than 85%, satisfying the need for hole cleaning. The success in completing the well indicted that the formulated drilling fluid had solved the problems previously existing in the area.