In the last few years, several accidental events have highlighted the importance of major manmade hazards, either accidental or deliberate by nature, within chemical and process facilities. Moreover, many plants are located in unstable geo-political areas, where the risk of major accidents triggered by external factors, such as terroristic attacks or sabotages, is not negligible. Hence, intentional risks should be investigated by proper risk assessments, included in the risk picture and reduced by applying adequate security measures. Because of the increased attention for security issues, optimal selection of security measures, by developing and applying economic analyses, may become more important to reduce plants vulnerability towards intentional malevolent acts, as terroristic attacks and sabotages. Despite economic models, such as cost-benefit analysis for supporting the decision-making process, have proved to be fundamental in many respects with regards to safety, for instance no specific applications of cost-benefit analysis are available in the security domain, within the chemical and process industry context. In this paper, the role of the fundamental terms of cost-benefit analysis within the specific framework of process-industry security is discussed, focusing on the estimation of the threat probability, the assessment of physical security systems costs and performances and the evaluation of the costs of the losses derived from either perspective or retrospective accidental scenarios. Furthermore, a cost-benefit analysis was applied to an illustrative case study, based on a hypothetical sabotage to a storage tank in a process facility, leading to a major accident. The aim of the case study is to prove that the application of cost-benefit analysis provides an economic aid or criterion for selecting additional security measures in a process plant. Starting from a credible sequence of adversary’s actions, the uncertainties related to the threat probability have been accounted and realistic security measures in place have been considered, determining the baseline physical security system performance. Therefore, three pertinent security upgrades have been proposed; for each of them the performances improvement and realistic total costs have been calculated; the losses derived from an expected accidental scenario have been estimated. Then, cost-benefit analysis has been applied proving that it allows defining a rational allocation of security measures. Therefore, we conclude that cost-benefit analysis may offer a relevant support in security risk analysis and its related decision-making process, within the chemical and process industry domain.