Two novel small-molecules PO-PhQ and PO-PhQNO, in which both polar phosphine oxide (PO) and N–oxide (NO) groups are incorporated in phenyl quinolone core unit were synthesized as efficient cathode interfacial layers (CILs) for inverted organic solar cells (IOSCs). Because of the phenylquinoline (PhQ) group, both PO-PhQ and PO-PhQNO are endorsed with high electron mobility. Due to the presence of polar P=O and N-oxide groups in their molecular structure, PO-PhQ and PO-PhQNO possess good solubility in polar solvents which make them as suitable candidates for interfacial modification of solution processed multilayer IOSCs. As a result, the power conversion efficiency (PCE) of the inverted devices based polythieno[3,4-b]-thiophene-co-benzodithiophene (PTB7):(6,6)-phenyl-C71-butyric acid methyl ester (PC71BM) active layer with PO-PhQ and PO-PhQNO as CILs achieve PCE values of 9.03 and 8.53%, respectively, with 10–16% improvement than that of the control device with ZnO. In addition, both PO-PhQ and PO-PhQNO make certain the IOSC devices with long-term stability. To the best of our knowledge, this is the first time that cathode interfacial materials based on the combination of PhQ and P=O groups is reported. The effective application of these alcohol solution processed CILs indicate that the lending P=O to PhQ could be very promising strategy in developing high performance and eco-friendly solar cells. Our findings would contribute to enhancing the OSC device performances from synthetically view point of designing new materials.