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ABSTRACT Zhu, T.; Dai, X., and Ai, F., 2018. Design of drilling fluid of high temperature and high pressure resistance in well drilling of deepwater area. In: Liu, Z.L. and Mi, C. (eds.), Advances in Sustainable Port and Ocean Engineering. Journal of Coastal Research, Special Issue No. 83, pp. 62–67. Coconut Creek (Florida), ISSN0749-0208. On the basis of routine deepwater drilling fluid HEM system, the high temperature and high pressure drilling fluid system for drilling of profundal zone was built by optimizing the low temperature resistance hydrate inhibitor and high temperature resistance fluid loss additive. The laboratory evaluation showed that the constructed drilling fluid system had good low-high temperature rheological characteristic, anti-pollution capacity, settlement stability, sealing pressure-bearing and reservoir protection. This drilling fluid system had been successfully used in 25-1S-1 deepwater high Temperature and high pressure wells in the western South China sea. It could avoid the complex situation such as well leakage and overflow. The operation efficiency was improved. It had great popularization and application value.