Purpose: The purpose of this study was to assess pain, sleep disturbance, fatigue, and the quality of life and to identify the impact of pain, sleep disturbance and fatigue on the quality of life in patients with pancreatic cancer undergoing chemotherapy. Methods: Data were collected from June to July, 2010. Participants were recruited from Y university hospital in Seoul. Research instruments included numeric rating scale for pain, Functional Assessment Chronic Illness Therapy-Functional Well-Being (FACIT-FWB): General Factor 5 (GF5) for sleep disturbance, Functional Assessment of Cancer Therapy-General (FACT-G) for quality of life, and FACT-Fatigue for fatigue. Results: The quality of life for cancer patients had a significant relationship with pain, sleep disturbance, and fatigue. The significant factors influencing quality of life were pain, sleep disturbance, and fatigue that explained 52.6% of the variance. Conclusion: Patients with pancreatic cancer undergoing chemotherapy experienced pain, fatigue, and sleep disturbance which led to a negative effect on quality of life. The results suggest that intervention program to improve quality of life could reduce pain, fatigue, and sleep disturbance of pancreatic cancer patients undergoing chemotherapy.