Nowadays, covalent organic framework (COF) has shown great potential in chromatographic separation, and enriching the design of novel COF based stationary phases and broadening their application prospects remains of great significance. Microporous organic network (MON) is a novel type of porous material with large specific surface area and excellent stability connected by covalent bonding, which is extremely similar to COF. Especially, nano-sized MON has the characteristics of easy binding with silica matrix and superior chromatographic separation performance. In this work, the combination of MON and COF as the surface modification materials of silica gel was first explored. The conjugated network structure of MON and COF can improve the permeability of silica stationary phase, and the presence of abundant functional groups in COF and MON can enhance the separation ability for a series of aromatic compounds. Moreover, hydrophilic L-cysteine containing thiol group was cleverly introduced into MON/COF@SiO2via thiol-ene/yne click reactions to balance the hydrophilicity and hydrophobicity of stationary phase. The L-cysteine modified chiral MON/COF@SiO2 (CMON/CCOF@SiO2) was used for effective separation of various chiral/hydrophilic/hydrophobic analytes, and the CMON/CCOF@SiO2 was observed to exhibit superior separation ability to the CCOF@SiO2. Multi-mode chromatographic separation mechanisms were explored, demonstrating that multiple interactions were involved in the separation process. Finally, the CMON/CCOF@SiO2 was applied to detect the environmental endocrine disruptors in the water sample and pyridoxine in the tablet sample, respectively, indicating a great potential for application in actual sample detection.