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Objective: The objective was to investigate the relationship between the coping strategies used and the perception of quality of life in adolescents diagnosed with oncological diseases, highlighting the impact of psychosocial factors on emotional adaptation to the disease. Method: The research was conducted on a sample of 20 adolescents (12 boys, 8 girls), aged between 12 and 18 years, hospitalized in a pediatric oncology unit. Participants completed two validated instruments: PedsQL (oncology version) to assess quality of life and the KidCOPE questionnaire to identify coping strategies used. Results: The mean global quality of life score was 70, indicating a moderate-good quality of life. The highest scores were recorded for communication and anxiety towards treatment, and the lowest for pain and procedural anxiety. The most frequently used coping strategies were emotional and avoidant, such as distraction, social withdrawal, and acceptance. Problem-focused coping was less common, indicating a need for educational interventions. Regression analysis showed that coping dimensions explained about 26% of the variance in adolescents’ quality of life, with avoidant coping emerging as a significant negative predictor. Discussion: Adolescents with cancer demonstrate a functional capacity for adaptation despite medical and emotional challenges, benefiting from good relationships with the medical team and social support. However, the predominance of avoidant strategies indicates a potential imbalance in long-term emotional regulation. Conclusions: The results highlight the importance of integrating psychological and educational interventions focused on developing active coping strategies and supporting the resilience of adolescents with cancer, in order to optimize their quality of life.