The predator-prey relationships between juvenile Nile Tilapia Oreochromis niloticus and native fish species of the Paraná River basin, Brazil, were experimentally examined. Juveniles of O. niloticus were offered to three native predator species (Salminus brasiliensis, Pseudoplatystoma corruscans, and Brycon orbignyanus) in 2,000-L tanks with four levels of habitat complexity (0%, 50%, 100% and RD (rocks and driftwood)). Predator efficiency was more variable among species (S. brasiliensis consumed 86.6% of the prey, P. corruscans 22.5% and B. orbignyanus 18.3%) than among levels of habitat complexity, and S. brasiliensis was faster than the others in detecting and consuming the prey. The higher predatory efficiency observed for S. brasiliensis can be partially explained by its more aggressive behavior (it fed earlier and for longer) and its presence in the surface layer. Here, the presence of predators led to O. niloticus juveniles spending more time at the surface or remaining in schools to coexist at the bottom with the predators, as expected for cichlids under predatory pressure in natural environments. Our results suggest that preserving and restoring populations of S. brasiliensis (and also to some extent P. corruscans and B. orbignyanus) might help to control O. niloticus in the Paraná River basin.