Objective This study examined whether cancer-specific coping strategies have any significant influence on the quality of life of 205 women living with breast cancer in Ghana. Methods Using a cross-sectional survey design, participants were administered questionnaires which measured their cancer-specific coping strategies and health-related quality of life. Results Correlation analysis showed that helplessness-hopelessness negatively correlated with physical wellbeing, emotional wellbeing, functional wellbeing, and breast cancer additional concerns. Anxious preoccupation negatively correlated with all the domains of quality of life, whereas fighting spirit was positively correlated with emotional and functional wellbeing. Cognitive avoidance was positively correlated with functional wellbeing, while fatalism was positively related with all the domains of quality of life. Regression analysis revealed that anxious preoccupation predicted significant decreases in all the domains of quality of life, while helplessness-hopelessness predicted significant decreases in emotional and functional wellbeing domains. However, cognitive avoidance predicted significant increase in the functional domain of quality of life. Conclusion These findings underscore the need for psychosocial support for breast cancer patients to adopt effective coping strategies to deal with their challenges in managing their illness.