Background. Quality of life and responsibility are known as fundamental issues in contemporary psychology. Therefore, this study aimed to investigate the effect of problem solving training on quality of life and responsibility of paramedical students of Tabriz University of Medical Sciences. Methods. The present study was a quasi-experimental study with a pre-test-post-test design. The statistical population of the study consisted of all paramedical students (490 students) in the academic year 2020-2021 in one of the ranked universities. The available sample was randomly divided into an intervention (n = 20) and a control group (n = 20). The Quality of Life Questionnaire (SF-36) and Gauff Responsibility Questionnaire were used to collect data. Problem-solving training, using scenario, was provided for the experimental group in the form of 2-hour sessions held twice a week for a period of 14 weeks. The data were analyzed, using co-variance analysis and SPSS 21 software. Results. The mean age of the participants was 20.61 in the intervention, and 21.21 in the control groups. The standard deviation calculated for the two groups were 1.14 and 1.62, respectively. The problem solving training seemed to enhance the scores on the quality of life [F(1,39)=1052.192, P<0.001, ƞ2=0.966] and students’ sense of responsibility [F(1,39)=126.111,P<0.001,ƞ2=0.773] Conclusion. The results of testing the research hypotheses showed that problem solving training has a significant positive effect due to the knowledge of problem solving skills, reducing the incidence of mental illness in students. Therefore, it is recommended this approach be used to promote students' mental health