The purpose of this study was to analyze the moderated mediation effect of acculturation stress through career decision-making self-efficacy in the relationship between social support and career adaptability of North Korean defectors. To this end, social support, career decision-making self-efficacy, acculturation stress, and career adaptability were measured through online and offline surveys. To do this, 151 North Korean defectors (male: 44, female: 107) in their 20s through their 60s who live in Korea participated. The collected data were subjected to a correlation analysis and a hierarchical regression analysis and were assessed using the PROCESS macro through SPSS 22.0. The results of this study are as follows. First, career decision self-efficacy had a partial mediating effect in the relationship between social support perceived and career adaptability. Second, there was a moderating effect of acculturation stress in the relationship between career decision self-efficacy and career adaptability. Finally, in the relationship between social support and career adaptability, the mediating effect of career decision self-efficacy was found to be controlled by acculturation stress. These results suggest the need for a policy support plan that improves the career adaptability of North Korean defectors from both long-term and short-term perspectives.