Depression is the most common mental health problem reported among dialysis patients. Problem-Solving Therapy (PST) is effective for treating depression in patients with chronic illness, but its acceptability has never been reported in older hemodialysis patients, and its association with health-related quality of life is unknown. We investigated the feasibility and effectiveness of PST in HD patients by assessing changes in depressive symptoms and health related quality of life after six weeks’ PST therapy at a single, hospital-based chronic hemodialysis unit in central Pennsylvania. Thirty-five patients were randomly assigned to either six weekly sessions of PST-Usual Care or Usual Care. Depression, quality of life, and problem-solving ability were measured at baseline and post-treatment. Thirty-three subjects completed the study; one subject died and one subject withdrew due to illness (both randomized to the PST intervention group). At baseline, subjects in each arm were similar except that patients in the intervention group were more likely to have a history of depression (control group (16.6%), intervention group (53.5%). At six weeks, there were no significant differences in mean PHQ and BDI scores between the groups; however, mean change-from-baseline scores were significantly improved in the intervention group relative to the control group. When adjusted for baseline depression scores, mean 6-week BDI and PHQ scores were significantly lower in the intervention group. Results of this pilot study suggest that PST provided to maintenance hemodialysis patients on-site holds promise for reducing depressive symptoms, though more extensive studies need to be conducted.