Copper (Cu) mining in Minas do Camaquã-Brazil, released significant amounts of metals into the João Dias creek, where Hyphessobrycon luetkenii inhabit. Because the involvement of Cu in biological processes its concentration and availability is regulated by molecules as the metal regulatory transcription factor (MTF-1), metallothionein (MT) and transporters (ATP7A and CTR1). These genes were whole sequenced and their expression (GE) evaluated in gills, liver and intestine. Were collected fish in non-contaminated and contaminated (Cu 3.4-fold higher) sites of the creek (CC and PP) and respectively translocated (CP and PC) for 96?h. The GE of the non-translocated groups evidenced that MT, MTF-1 and CTR1 have organ specific differences between both communities. Additionally the translocation allowed to identify organ specific changes associated with the activation/inactivation of protective mechanisms. These findings indicate that MTF-1, MT and CTR-1 GE play an important role in the tolerance of H. luetkenii to Cu contamination.