This is a cross-sectional descriptive study that investigates the mediating effect of humanism on the relationship between task performance and holistic nursing competence among clinical nurses. The participants were nurses with more than one year of work experience in general hospitals in South Korea, recruited using convenience sampling. A total of 227 data samples were collected. A self-reported questionnaire including the task performance competence scale, holistic nursing competence scale, and humanism scale was used for the survey. Data were analyzed using thet-test, analysis of variance, Pearson’s correlation coefficients, and hierarchical multiple regression after checking for normal distribution. The results showed that task performance competence, holistic nursing competence, and humanism differed according to characteristics such as gender, age, educational level, marital status, position, length of career, and job and salary satisfaction. Task performance competence was positively correlated with holistic nursing competence and humanism. A positive correlation was also observed between holistic nursing competence and humanism. A partial mediating effect of humanism in the relationship between task performance competence and holistic nursing competence was confirmed. Thus, to increase nurses’ holistic nursing competence, it is necessary to improve task performance competence and formulate a continuous and repetitive education program that includes humanism.