Fatigue life in critical parts of structure components, which is subjected to variable amplitude loading, is a very complex subject. When a fatigue life is influenced by these load variations, accelerations and/or retardations in crack growth rate can occur. Thus, an accurate prediction of fatigue life requires an adequate evaluation of these stress interaction effects. There are many different indexes for calculating fatigue damage at critical locations. The crack severity index based on crack growth is one of the methodologies implemented for modern military aircrafts to define mission severity relative to a known reference usage. But, this index cannot consider stress interaction. In this study, a novel index was proposed to evaluate an effect for stress interaction by using entropy concept, and fatigue life prediction methodology was developed by using entropy index of stress interaction and crack severity index of effective stress.