Potato (Solanum tuberosum L.), a plant of great economic importance worldwide, is known to be highly sensitive to salinity. Improving the tolerance of this crop was envisaged using interspecific somatic hybridization. In this report, the impact of salinity on three hybrid lines (STBa, STBc, and STBd) produced by protoplast fusion between the cv. BF15 and the wild species Solanum berthaultii was investigated in vitro. An analysis of plant response to oxidative stress was considered when plantlets were submitted to 100 mM NaCl for 5 d. The peroxidation of membrane lipids was screened by measuring malondialdehyde accumulation in these lines. Moreover, gene expressions and activities of antioxidant enzymes, such as catalase (CAT), peroxidase (POX), and superoxide dismutase (SOD), were assessed. The results show a lower degree of lipid peroxidation in the hybrid lines in comparison to the BF15 parent. These hybrids also showed higher activities of CAT, POX, and SOD than the BF15, especially in roots. The significant inductions of FeSOD, (Cu-Zn)SOD, MnSOD, and CAT genes in hybrid plants suggest their participation in salt tolerance. The differential expressions of the SOD and CAT genes between leaves and roots also indicate their tissue specificity.