Reduced imine cage (RCC3) was first adopted for the preparation of porous organic cage embedded C18 amide silica stationary phase for high performance liquid chromatography. The prepared stationary phase was characterized by scanning electron microscope (SEM) and Fourier transformation infrared spectrum (FT-IR). Its chromatographic performance under reversed-phase mode was investigated in detail and compared with that of an ODS column. Multiple interactions, including hydrophobic interaction, π-π interactions, electrostatic interactions and hydrogen bonding, were involved due to the synergism of the C18 chain and RCC3. The column showed typical methylene selectivity and enhanced aromatic selectivity for nonpolar analytes while demonstrating high selectivity for polar analytes. In addition, the stationary phase showed the capability of separation of polar and hydrophilic compounds under per aqueous liquid chromatography mode (PALC), providing a green and economical way for the separation of polar and hydrophilic compounds. These results indicated the great application potential of the prepared stationary phase in the analysis of complex samples.