Background: Chronic kidney disease (CKD) and End-stage renal disease (ESRD) is a prevalent and important non-communicable condition that poses a long-term global health burden. In Saudi Arabia, the previously available literature on the topic does not present sufficient evidence to produce sound guidelines for a better outcome and healthier life for the patients on hemodialysis. Objective: To assess the prevalence of anxiety and depression and its related influencing factors among CKD and ESRD patients on hemodialysis at the dialysis unit of King Khaled and the Military hospital in Al-Kharj city. Methodology: A cross-sectional study of Al-Kharj city’s major hospitals was conducted from December 2016 to January 2017. The study included 144 CKD and ESRD patients on hemodialysis using a stringent set of inclusion and exclusion criteria. A standard self-administered questionnaire-the Hospital Anxiety and Depression Scale (HADS) was used in the study to measure the presence and severity of anxiety and depression in the study population. Appropriate statistical tests were used to identify associations between relevant factors and anxiety/depression. Results: Results were collated from 116 patients. There were 66 males and 50 females with a mean age of 52.33 ± 16.17 years. Overall, 12%, 4.31%, 27.6%, and 23.3% of patients reported borderline anxiety, abnormal anxiety, borderline depression, and abnormal depression, respectively. Conclusion: The present study does not provide a statistically significant association between anxiety/depression and hemodialysis; however, anxiety and depression should be investigated among the patients on hemodialysis as these disorders commonly coexist with CKD and ESRD, and they affect the quality of life.