Abstract: SK-2 Well, supported by ICDP (International Continental Drilling Program), is the first continental scientific exploratory well in the world which penetrates the continental Cretaceous sedimentary formations. In the second spud (2 840 m), the total clay minerals of illite/smectite layer, illite and kaolinite in the formations encountered by the well was up to over 60%, which are easily hydrated, leading to tight hole and collapse. The upper casing in 2nd spud was ?508 mm, and the lower hole size was ?215.9 mm. The large difference between the upper and lower holes led to difficulty in flowback of cuttings. Through mineral identification by XRD diffraction, indoor compounding of drilling fluid materials and experiment on field core soaking, the low-cost drilling fluid system was selected which was applicable to coring in large holes of ?311.2 mm and ?215.9 mm. In field application, the ratio of dynamic shear force of drilling fluid was maintained at 0.45 to 0.82 Pa/(mPa·s), the lubricating coefficient was controlled at 0.11 to 0.14, and sticking coefficient of filter cake was 0.12 to 0.15, which effectively addressed the problems of carrying cuttings and reduced the risk of stuck pipe in long open hole. No large collapsing and sloughing occurred downhole during frequent alternating of coring test in large hole, formal designed coring and non-coring drilling jobs and during continuous conditioning of drilling fluid properties, and the experiments of ?311.2 mm core drilling in 491.12 m to 510.94 m and ?215.9 mm core drilling in 1 074.00 m to 1 148.01 m and 1 182.74 m to 1 256.01 m as designed were successfully completed.