Background Modern treatment for multiple myeloma (MM) has improved disease control and prolonged survival; thus, maintenance of quality of life (QoL) is considered a great concern for MM patients and their caregivers. The purpose of this study was to identify dyadic associations between stress appraisal and the QoL of patients with MM and their caregivers in Korea. Methods A total of 102 MM patient‐caregiver dyads participated in this study. They independently reported their stress appraisal and QoL. The study was guided by a transactional model of stress and coping, and analyzed by using the actor‐partner interdependence model. Results The results revealed good data adjustment with acceptable indices: χ2 = 6.211 (df = 6), CFI = 0.999, TLI = 0.994, RMSEA = 0.019, and SRMR = 0.043. MM patients' QoL were significantly correlated with caregivers' QoL. The stress appraisals of patients and caregivers mutually influenced each other's QoL. The patients' illness perception and the caregivers' burden were strong predictors for their QoL. The self‐efficacy of patients and caregivers was also associated with their QoL. Conclusions Our findings suggest that the way patients and caregivers perceive and respond to stress plays a significant role in their QoL during the treatment experience. Interventions designed to reconstruct negative perspectives and improve self‐efficacy may help both patients and caregivers to improve their QoL.