The aim of this study is to determine the relationship between self-regulation and 21st century skills of preschool children and the effect of self-regulation on 21st century skills. Relational survey was used as the research model. The sample of the study consists of 217 children studying in kindergartens in Tarsus district of Mersin province in the 2022-2023 academic year. The Self-Regulation Skills Scale was used to measure children's self-regulation skills and the 21st Century Skills Scale for 5-6 Year Old Children (DAY - 2) was used to measure 21st century skills. Correlation analysis and structural equation modeling were applied to the data. According to the findings, it was determined that there was a significant relationship between children's self-regulation and 21st century skills and their sub-dimensions. In the structural equation model, it was concluded that self-regulation significantly affected 21st century skills and explained 45% of the total variance. The findings obtained during the research process were discussed within the scope of the relevant literature and suggestions were made for future studies.