Metal bioaccumulation and metallothionein (MT) expression were investigated in gills and liver of the red-blooded Antarctic teleost Trematomus hansoni with the aim to evaluate the possibility for this species to face, with adequate physiological responses, an increase of copper or cadmium concentrations in the environment. Specimens of this Antarctic fish were collected from Terra Nova Bay (Ross Sea) and used for a metal exposure experiment in controlled laboratory conditions. The two treatments lead to a significant accumulation of both metals and an increase of gene transcription only for the MT-1. The biosynthesis of MTs was verified especially in specimens exposed to Cd, but the majority of these proteins were soon oxidized, probably because they were involved in cell protection against the risk of oxidative stress, by reactive oxygen species scavenging. The obtained data highlighted the phenotypic plasticity of T. hansoni, a species evolved in an environment characterized by natural high concentrations of Cu and Cd, and maybe the possibility for the Antarctic fish to face the challenges of a world that is becoming every day more toxic.