Stress in medical students is caused by tenacious medical programs, which may have physical and psychological effects on the quality of life of medical students. The study aimed to examine the relationship between self efficacy and quality of life in medical students. In addition, we examined the mediation role of perceived stress on relationship between self efficacy and quality of life. The study was conducted on hundred medical students ( 64 male and 36 female) of Institute of medical sciences, Banaras Hindu University, Varanasi in the age range of 19 to 22 years ( Mean age= 20.36, SD= 1.26). The data was collected by using the self efficacy scale (Sud et al, 1992), perceived stress scale (Cohen et al 1983) and WHOQOL-26 BRIEF. Results showed that most of the dimensions of QOL as well as the total scores of QOL were correlated positively with self efficacy and negatively with perceived stress. To examine the mediation role of perceived stress in self efficacy-QOL relationship a mediation analysis was carried out. In the total sample, self efficacy predicted QOL in an initial regression model (beta = 0.37, p< 0.001). When perceived stress was added to the model, however, self efficacy was attenuated less and insignificant (beta = 0.11, NS). A Sobel test of significance confirmed a mediated effect (p<0.01). Self efficacy is associated with QOL in medical students, and this relationship is mediated by perceived stress.