Interbedded sand-mud stones are developed widely in the F reservoir of the Songliao Basin, and kaolinite and illite are main clay minerals in the F reservoir, which are very important for the physical property and the effective development of the reservoir. The study of the 90 pieces of natural cores shows that both permeability and porosity of the F reservoir increase with the increase of kaolinite relative content and decrease with the increase of illite relative content. Sand-stone layer has good permeability and high kaolinite relative content, and in this layer secondary illite seldom deposits in-situ, resulting in the existence of large amounts of erosion pores. In contrast, the mud-shone layer has poor permeability and high relative content of illite. Moreover, the fiber-style existence of illite and book-stack-style existence of kaolinite make the sand-stone permeability much better and the mud-stone permeability much worse. The effect of kaolinite and illite on the reservoir physical properties can be detected by in-house core flow experiments. The results show that the F reservoir has a medium but slightly weak velocity sensitivity and a medium but slightly strong alkaline sensitivity, and that the velocity sensitivity of the reservoir will increase with the increase of kaolinite and illite absolute content, and the alkali sensitivity will increase with the increase of kaolinite absolute content but has no relationship with the illite content. More attention should be paid to the kaolinite-oriented velocity and alkaline sensitivity, for the relative content of kaolinite approximates half of all clay content in this reservoir.