End-stage renal disease (ESRD) is a common chronic disease worldwide that requires hemodialysis. Patients may face chronic pain and poor quality of life. Therefore, a better understanding of these variables in hemodialysis patients is essential to provide a good intervention. We aim to determine how common chronic pain is in hemodialysis patients and its correlation with sociodemographics, C-reactive protein (CRP), calcium, phosphorus, albumin, and parathyroid hormone. A cross-sectional study of hemodialysis patients was conducted in Palestine. Data collection took place between November 2020 and May 2021. We used the brief pain inventory score to assess chronic pain, and lab tests detected CRP levels. Data were collected using a convenience sampling technique. There were two hundred sixty-one patients in the present study. The mean age of the patients was 51 years, with 63.6% being men. 47.1% of them reported having chronic pain. Gender (p = 0.011), social status (p = 0.003), educational status (p = 0.010), and number of chronic diseases (p = 0.004) indicated a significant relationship with the severity score of pain. Furthermore, sex (p = 0.011), social status (p = 0.003), and number of chronic diseases (p = 0.002) were significantly associated with the pain interference score. Additionally, Person’s test indicated significant correlations between CRP and pain severity (p < 0.001) and with pain interference (p < 0.001). Albumin was significantly and negatively correlated with pain severity (p = 0.001) and pain interference (p < 0.001). Multiple linear regression analysis revealed that patients who had a higher CRP level and many chronic diseases were more likely to have a higher pain severity score. However, pain severity was the only predictor for pain interference. Our results suggest that there is a significant correlation between the existence of chronic pain in hemodialysis patients and increased CRP levels. However, further investigations are needed with a larger number of patients in more than one dialysis unit to confirm this correlation and management of chronic pain in patients with HD.