This research aims to examine the effect ofaudit knowledgeand Self Efficacy towards professional auditors skepticism. The independent variable in this study is audit knowledge and Self Efficacy. While the dependent variable in this study is skepticism of professional auditors. The population in this study were functional auditor officials and examiners at the Yogyakarta Regional Inspectorate Office. The technique used in sampling was convenience sampling technique and obtained 38 people who could be sampled. The method used in conducting data analysis is by using multiple linear regression analysis methods. Based on the results of data analysis that has been done, it shows that the audit knowledge variable is not aimed at the auditor's professional skepticism. While the positive self-efficacy variable towards skepticism of professional auditors.