Melanoma is an aggressive type of skin cancer, with the number of cases expected to increase in the future. The available treatments show low efficiency highlighting the need to develop new therapies to increase the survival of the patients. Beta-blockers, drugs already known and used for heart conditions; have shown anti-cancer properties and potential to be valuable in conjugation with chemotherapy. This study aimed to evaluate, in vitro, their potential for cancer treatment. A375 cells (melanoma cell line) were exposed to non-selective blockers (carvedilol and propranolol), β1 selective blockers (atenolol and metoprolol), and antineoplastics drugs (cisplatin and 5- fluorouracil), and viability assessed at 3 timepoints. Selective beta-1 blockers had no significant effects on cell viability. However, the other tested pharmaceuticals affected cell viability allowing the determination of median lethal concentrations (LC50) at 72h and a toxicity ranking: cisplatin (2.46 (1.87 – 3.38), 5-fluorouracil (4.77 (4.48 – 5.07)), carvedilol (16.91 (15.47 - 18.99)) and propranolol (58.03 (57.08 - 59.11)). Carvedilol and cisplatin were, respectively, the most toxic beta-blocker and antineoplastic. Following these results, a combined exposure of beta-blockers and antineoplastics was performed: cisplatin with metoprolol, propranolol, and carvedilol and also paired both non-selective beta-blockers. The results so far support the potential use of non-selective β-blockers as adjuvants of chemotherapy as a melanoma treatment.