Fatigue is a typical service failure mode when elastomers are subjected to cyclic loads over a period of time. Deformation gradient plays crucial role in fatigue behavior as elastomers exhibit nonlinear and linear characteristic under large and small deformations respectively. Also, in filled elastomers Mullins effect and hysteresis are another challenges. Natural Rubber (NR)/ Organoclay nanocomposites exhibit enhanced mechanical properties. However, degree of improvement is governed by the state of silicate layers dispersion and their extent of interactions with rubber segments. In the present work, attempts have been made to prepare NR/ Organoclay nanocomposites with intercalated/ and exfoliated nanostructure via melt mixing process. EpoxidizedNR (ENR) was employed as interfacial compatibilizer to modify the interface between NR segments and clay nanolayers. Strain controlled cyclic fatigue test was performed on both interfaciallycompatibilized and uncompatibilizednanocomposites. The alteration of microstructure during cyclic deformation was followed by XRD and hysteresis measurements. Reduced fatigue life was observed for both compatibilizedand uncompatibilized nanocomposites compared with unfilled NR at low strain amplitudes. Whereas, at high strain amplitudes enhanced fatigue resistance was exhibited byboth classes of nanocomposites which was consistent with higher hysteresis and delamination of silicate layers during periodic loading. However, uncompatibilized nanocomposites presented significant enhanced fatigue life compared to the compatibilized samples. Finally results have been modeled using fatigue crack nucleation model. Keywords: Fatigue behavior, Hysteresis, Microstructure, Compatibilization, Natural rubber, Organoclay, Nanocomposite,