Although obesity is an important risk factor for cancer incidence, the effect of body mass index (BMI) on health-related quality of life (HRQoL) after cancer treatment remains unknown. This population-based cross-sectional study assessed different levels of BMI as an important factor associated with impaired HRQoL in long-term cancer survivors. The study enrolled 1104 cancer survivors from the fourth to seventh Korea National Health and Nutrition Examination Surveys (KNHANES 2007-2018) who were alive at least 5years after their cancer diagnoses. The BMI was classified into four categories: < 20 (underweight), 20-22.9 (healthy weight), 23-24.9 (overweight), and ≥ 25kg/m2 (obese). Impaired HRQoL was defined as the lowest quartile of European Quality of Life 5-Dimensions (EQ-5D) questionnaire scores. Cancer survivors who were underweight or obese were more likely to report health problems on each dimension of the EQ-5D compared to the other BMI groups. In multivariate logistic regression analysis, the two extreme BMI categories were significantly associated with impaired HRQoL (BMI < 20kg/m2: odds ratio [OR] = 1.73, 95% confidence interval [CI] = 1.08-2.86; BMI ≥ 25kg/m2: OR = 2.14, 95% CI = 1.41-3.25; P trend = 0.049), especially in the gastrointestinal cancer group (P heterogeneity = 0.007). Moreover, the association between underweight/obese and impaired HRQoL showed a significant sex difference (P heterogeneity = 0.019). The results of this study suggest that deviations from normal BMI, such as being underweight or obese, are negatively associated with HRQoL in long-term cancer survivors; to some extent, this may depend on cancer type and sex. Reaching or maintaining a healthy weight should be emphasized for cancer survivors as a long-term goal even after cancer treatment.