Among the 14 million persons living in the United States with current or remitted cancer, poor physical health-related quality of life (HRQL) is a significant concern. However, self-compassion (i.e., common humanity, mindfulness, self-kindness) may be a protective factor, either directly or indirectly, by allowing for a sense of empowerment and control over illness, and in turn, facilitating engagement in treatment and positive perceptions of health. Serial mediation analyses among persons living with current (n = 67) or remitted (n = 168) cancer lend support for a positive, direct association between self-compassion and physical HRQL, as well as indirect effects via internal perceived control and, to a lesser degree, treatment adherence. Mixed findings, especially among cancer patients, highlight limitations of resiliency traits while also supporting the notion that self-compassion interventions (e.g., Mindful Self-Compassion Training) may have positive implications for health-related control beliefs, behaviors, and quality of life in the cancer population