The effects of cancer and its treatment on quality of life contribute to patient and clinician decisions. Health-related quality of life (HRQL) is a subjective concept, leading to variation in its definition. This presents challenges when measuring HRQL and evaluating interventions. The designers of the Patient Generated Index (PGI) addressed these challenges by having individuals identify areas of their lives affected by illness and treatment, then report on these self-defined areas. We used cognitive interviews to collect information about patient understanding of the PGI, the response processes used to complete the PGI, and how well the PGI reflected participant HRQL. Interview data support the content validity of the PGI in comprehensively defining and adequately sampling participant HRQL as an individualized construct. Findings also support our recommendation to revise PGI formatting to reduce response errors. We make recommendations to reduce the cognitive demands the PGI places on respondents.