Facing with the difficulty of specific chromatographic separation of nucleoside drugs, this study prepared a surface molecularly imprinted polymer (SMIP) modified covalent organic framework (COF) coated silica stationary phase based on the specificity of molecular imprinting technology and the powerful chromatographic separation performance of COF. This novel SMIP-COF@SiO2 stationary phase can not only specifically identify template molecule and structural analogs, but can also be used to separate multiple types of analytes, such as B vitamins, sulfonamides, alkylbenzenes, phenyl ketones, polycyclic aromatic hydrocarbons and environmental endocrine disruptors, which satisfies the need for complex sample separation. Various retention mechanisms have been investigated and multiple interactions between the SMIP-COF@SiO2 stationary phase and the analytes are discovered. The chromatographic performance of SMIP-COF@SiO2 is far superior to that of the SMIP@SiO2 and COF@SiO2. Furthermore, the SMIP-COF@SiO2 stationary phase can be successfully used to analyze polycyclic aromatic hydrocarbons in the environmental water sample and detect whitening ingredient in skincare product, indicating its great potential for application in various fields.