BackgroundPost-treatment pain has been suggested as an important indicator for health-related quality of life (HRQOL) in patients with breast cancer. Therefore, this study was performed to examine the association between pain and its impact on HRQOL among breast cancer patients in Palestine. Also, this study aimed to determine the QOL profile for breast cancer patients and stated the factors associated with QOL.MethodsA correlational cross-sectional study was conducted from May 2016 to November 2016 at Al-Watani Hospital and An-Najah National University Hospital in the Nablus district in Palestine. The five-level EuroQol five-dimensional instrument (EQ-5D-5L) was used to examine HRQOL. Pain severity and interference were assessed using the Brief Pain Inventory (BPI). Multiple linear regression analysis was performed to determine the most important variables related with HRQOL.ResultsOne hundred and seventy patients were involved in this study. Overall, all participants were female, with a mean ± SD for age of 51.71 ± 11.11 years. The reported HRQOL of this study was measured by using the median EQ-5D-5L index score, which was 0.67 (interquartile range: 0.51–0.84). There were moderate negative correlations between EQ-5D-5L index score and pain severity score (r = − 0.58, p value < 0.001), and pain interference score (r = − 0.604, p-value < 0.001). Furthermore, univariate analysis showed that age, marital status, employment status, income, current condition of cancer, and post-treatment pain were associated with quality of life (p-value < 0.05). Regression analysis revealed that patients with high income (p-value = 0.003), patients with lower pain severity score (p-value < 0.001), and lower pain interference score (p-value = 0.018) were independently associated with high QOL.ConclusionsThis is the first study to present important data regarding QOL by using the EQ-5D-5L instruments that may help healthcare providers to identify patients at risk of low QOL. Healthcare providers and health strategy makers should be alerted to low level HRQOL among breast cancer patients with low income level, patients with post-treatment pain, especially in the state of severe pain, and the state of pain interfering with daily life to improve their HRQOL.