Melanoma is the most lethal type of skin cancer showing an increasing incidence particularly in the young population, with a low 5-year overall survival rate of metastatic patients. Nevertheless, mortality has declined greatly with the advent of molecular targeted therapy and immunotherapy. Many of these approaches come with major side effects and high costs, making them not universally available, and emphasizing the need for new cost-effective therapeutic strategies. Bacterial-based immunotherapies are a rapidly emerging field that offers unique advantages in the fight against cancer. Unlike conventional cancer treatments, which have limited specificity for tumors, certain bacteria have been found to selectively colonize and exert direct oncolytic effects, as well as stimulating the immune system. Intratumoral inoculation of attenuated Salmonella exhibits antitumor activity in many cancer models, including melanoma. However, the molecular bases of this activity remain partially elusive. In this work we aim to dissect bacteria-induced changes in melanoma cells protein expression immediately after auxotrophic Salmonella LVR01 infection through comparative mass spectrometry.