This article was aimed to study the correlation between microstructure and stability of cream contained Span and Tween as compound emulsifier by factor analysis. Techniques such as microscopic observation and rheolog-ical examination were used to perform the microstructure. And the thermal analysis and near-infrared stability ana-lyzer was carried out to quantify characterization of the physical stability of cream. The results showed that among the series of S60-T80 and S60-T60 creams based on compound emulsifier, cream conductivity increased and more and more spherical lamellar liquid crystalline structures appear on micrographs with increasing Span 60 fraction. The greatest viscoelastic was appeared when the mass ratio of Span and Tween was 2:2 and 1:3, respectively. From the thermogravimetric analysis, the increase of Span 60 fraction led to the weight loss of samples between 50℃-70℃ in-crease, but it decreased within 70℃-110℃. It was concluded that there was positive correlation between the intensi-ty of microstructure and the ability of resistance to structural failure when the experiment conditions were stable. It had negative correlation with the hydrophilic gel phase water distribution index.