Collaborative problem-solving competence (CPSC) is a core skill in the twenty-first century. As an innovative literacy, CPSC was assessed for the first time in the Program for International Student Assessment (PISA) 2015. Our study aims to identify the effects of student’s perceptions toward interpersonal relationships on CPSC in PISA 2015. Multiple linear regression was used to examine these effects across Hong Kong, Macao, Taiwan, and the four affluent communities in China. After controlling student’s gender and socio-economic status, the results indicated that: (a) Student’s external perceptions such as teacher unfairness and disciplinary climate, and student’s internal perceptions such as valuing relationships and valuing teamwork significantly predicted CPSC; (b) Disciplinary climate was the strongest predictor among all the external perceptions analyzed; (c) Regarding the internal perceptions, valuing relationships positively predicted CPSC, while valuing teamwork negatively predicted CPSC. These findings enlighten educational practitioners to help students develop their CPSC from the perspective of interpersonal relationships.