Background Children's hand skills when performing in real‐life contexts have been commonly thought as a possible determinant of their self‐care function; however, there is a paucity of research investigating this potential predictive relationship. The purpose of this study was to provide evidence regarding whether children's real‐life hand skill performance is contributive to or predictive of their self‐care function by considering other child and cultural factors. Methods A total of 139 typically developing children and 114 with disabilities, ages 2–12 years from Australia and Taiwan, participated in the study. The outcome measures used were the Assessment of Children's Hand Skills (a measure of real‐life hand skill performance) and the Personal Living Skills subscale of the Vineland Adaptive Behavior Scales – Classroom Edition (a measure of self‐care function). Results Hierarchical regression analysis revealed that the children's demographic variables (age, gender, disability status, handedness and cultural context) accounted for 43% of the variance of the self‐care function in the combined group of children with and without disabilities. Age, presence of disability and cultural context were the statistically significant independent factors. However, after the entry of the real‐life hand skill performance factor, the contributing values of age and disability status decreased and the age factor became non‐significant. The hand skill performance factor was found to be the strongest, and its addition led to significant increments of 24.6% of the explained variance for children's self‐care function. Similar results were also found in the regression analyses based on separate groups of typically developing children or those with disabilities. Conclusions The findings provide evidence that children's real‐life hand skill performance is a contributing factor of their self‐care function. The assessment of children's hand skill performance in real‐life contexts is therefore needed.