Knowing how cave lithology influences the benthic macroinvertebrate fauna is important for conservation and management of subterranean aquatic systems. However, those influences are still poorly understood, especially in the Neotropics. This study aimed to understand how cave lithology can influence benthic EPT assemblages by assessing the differences in the EPT genera structure in caves of two distinct lithologies (quartzite and limestone) and determining possible differences in the lithology habitats. To achieve this, hydrochemistry data and biological samples were collected in six allogenic cave streams from the two aforementioned lithologies. Results showed that both the assemblages from different lithologies and within the same lithology are statistically different, thus indicating probable regional influences beyond local ones. Our results also pointed out an effect of lithology on the substrate parameters, which in turn affected the EPT composition. Cave lithology affects water chemical and physical characteristics, thus supporting different EPT assemblages. The results of this study provide a foundation for future investigation on how the lithology can influence the benthic macroinvertebrate fauna and should lead to means of predicting such fauna on the basis of the cave lithology and water chemistry.