Background: Frailty in cancer survivors poses a great challenge to health care providers. Frailty is associated with premature mortality, functional decline, and poor quality of life (QOL). We aimed to examine the associations of frailty and pre-frailty with physical functional performance and QOL in breast cancer survivors and bone marrow transplant (BMT) survivors. Methods: 43 breast cancer survivors and 55 BMT survivors who had received chemotherapy and did not have active cancer were recruited to the study. Based on Fried frailty phenotype, survivors were classified as frail if 3 or more criteria were present: unintentional weight loss, exhaustion, slow walking speed, low physical activity, and weakness. Pre-frail was classified if 1 or 2 criteria were present. Physical functional performance was assessed by Karnofsky performance scale (KPS) and continuous summary performance score (CSPS, comprises walking speed, standing balance, and repeated chair stands tests). p16^INK4a, a marker for cellular senescence, was measured from survivors’ blood samples. QOL was measured using the 36-Item Short Form Survey. Groups were compared using chi-square test for categorical variables and rank-sum test for continuous variables. Results: Median age of survivors was 59 yrs (39% male). 13% of survivors (N = 13) were frail and 26% (N = 25) were pre-frail. Frail/pre-frail survivors tended to be older, male, and BMT survivors and had worse results for KPS, walking speed, repeated chair stands, and CSPS (p-values<0.03). Frail/pre-frail versus non-frail survivors had a higher p16^INK4a expression (p-value<0.01). For QOL, frail/pre-frail survivors had lower median scores of physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, social functioning, bodily pain, and general health (p-values<0.04), but the median scores of emotional well-being for frail/pre-frail and non-frail survivors were similar (p-value=0.06). Conclusions: Frailty and pre-frailty in a study of breast cancer and BMT survivors were associated with worse physical functional performance, higher p16^INK4a expression, and lower quality of life.