Abstract: Well Nuo-1, 5 000 m in depth, is a key exploratory well located in the east of the northern margin (Quanji anticline, Huobuxun sag, Sanhu depression) of the Qaidam Basin. Formations penetrated by the well included strongly water-sensitive mudstones and frequent interbeds of sandstones and mudstones. Faults are developed in the area and formation saltwater renders contamination to the drilling fluids used. Difficulties in drilling fluid operation existed because of the problems and no offset well data were available for reference. An amine-based silanol highly inhibitive plugging drilling fluid was selected to inhibit the hydration and swelling of shale, and techniques for drilling fluid maintenance were optimized to inhibit the hydration and swelling of mudstone and shale formations, thereby to stabilize the borehole wall. The drilling of Well Nuo-1 was successful, providing a technical support for subsequent drilling operation in the same area. When drilled to the designed depth of each interval and the completion depth of the well, viscous mud was spotted at the bottom of the well to guarantee the success of casing running and well cementing. 10 times of well logging were all conducted successfully and casing strings were run to the bottom with no hindrance. Average percent hole enlargement of the φ444.5 mm was 7.46%, the φ311.2 mm was 9.33%, and the φ215.9 mm was 9.40%. Although pipe sticking had occurred drilling, these data indicate that the quality of the whole well is satisfactory, especially when the exploratory well was first drilled in an area that had never been explored. Average ROP of the well was 7.54 m/h, realizing the objective of "high quality fast drilling".