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Purpose: The aims of this study were to evaluate a hypothetical model explaining undergraduates’ interpersonal relationship ability associated with the stress of life, self-esteem, and their communication ability and to identify the mediating effect of a smartphone addiction tendency on the identified associations. Methods: Data were collected from 201 undergraduates using a structured questionnaire from August to September 2017. Data analyses included descriptive statistics, Pearson’s correlation coefficients, and structural equation modeling with SPSS AMOS 22.0. Results: The participants’ interpersonal relationship ability was 65.9%, explained by the stress of life, self-esteem, communication ability, and smartphone addiction tendency. The factors of undergraduates’ interpersonal relationship ability were self-esteem (β=.10, p<.01) and communication ability (β=.14, p<.001). Stress of life (β=.15, p<.01) directly affected the participants’ smartphone addiction tendency, which was not associated with interpersonal relationship ability. Conclusion: Based on our study findings, self-esteem and communication ability should be considered for developing nursing interventions to improve interpersonal relationship ability. However, a smartphone addiction tendency may be managed for undergraduates who experience excessive stress of life rather than interpersonal relationship ability. Thus, a tailored approach targeting specific needs or competence should be developed based on our data-based framework.