In this research, the surfactant-co-surfactant intermolecular interactions in the H 2 O-Oxyethylated Isononylphenol-Polyglyceryl-3 Methylglucose Distearate-Vaseline oil system were studied. For the first time, two approaches were combined: the additivity of hydrophilic lipophilic balance (HLB) and the water / oil interfacial tension measurement in microemulsion systems. It was shown that by calculating the HLB of the surfactant mixture and measuring the corresponding interfacial tension, it is possible to predict self-organization of surfactant. It was directly related to the intermolecular interaction estimated by calculating the interaction parameter It has been established that in mixed systems synergistic effects were observed and the interfacial tension decreased, which were caused by electrostatic attraction between surfactant's molecules. The processes of selforganization of surfactant mixture at the H 2 O-Vaseline oil interface were studied. It has been shown that the hydrophilic lipophilic balance of the mixture and the interaction parameter directly connected with the nature of the structures from liquid crystal to microemulsion. The proposed approach can be used for the scientifically based calculation of the components in the surfactant mixture at the liquid-liquid interface and prediction of microemulsion and liquid crystals formation in three component systems.