Raw pet food market is growing at rapid rate due to the raising perception as a natural option and the potential health benefits. However, raw pet food also may pose health concerns due to the occurrence of pathogenic bacteria such as Salmonella spp. High-pressure processing (HPP) is known as a non-thermal technology to inactivate microorganisms in food, preserving the nutritional characteristics with minimal impact on organoleptic traits. In this framework, the effects of pressure intensity (450–750 MPa), pressure-holding time (0–7 min) and lactic acid concentration (0–7.2 g/kg) on the inactivation of Salmonella spp. by HPP in chicken-based raw pet food intended for dogs was evaluated though a central composite design. Salmonella reduction ranged from 0.76 to > 9 log units depending on the combination of factors, which were all linearly correlated with inactivation. The rate of inactivation slowed down after an initial rapid drop of Salmonella levels during treatments, which was reflected as a quadratic term of holding time. The interaction between factors and the quadratic terms of pressure and lactic acid concentration were not statistically significant and therefore not included in the final model. According to the stochastic assessment, after treatments at 500 MPa for 4 min, the probability of a non-acidulated product being contaminated with Salmonella decreased to 0.03%. For these products, an increase in holding-time duration from 4 to 6 min at 500 MPa, decreased the probability of non-conforming products by approximately 50-fold. Remarkably, for products acidulated with 3.6 g/kg of acid lactic, the same increase in treatment duration reduced the probability of non-conforming products in approximately 475-fold. The results highlight the relevant influence of processing parameters and intrinsic factors associated with the product formulation (i.e. lactic acid causing a slight pH decrease) on the lethality of Salmonella in pressurized raw pet food. The polynomial model provided constitutes a useful decision-support tool for optimizing HPP of raw pet food, considering matrix acidulation by lactic acid as a strategy to enhance Salmonella lethality to comply with current regulations concerning pet food microbiological safety.