Purpose: The purpose of this study was conducted to identify the impact of Symptom Severity and Symptom Interference on Sleep Disturbance among cancer patients. Methods: This study was conducted from October 8th to October 25th, 2012. One hundred eight cancer patients were recruited from S city in Korea. The instruments used in this study were the Symptom Severity, Symptom Interference and the Sleep Disturbance scales for patients with cancer. Data were analyzed using descriptive statistics, t-test, ANOVA, Pearson correlation coefficients and multiple regression with the SPSS/WIN 20.0 program. Results: The Sleep Disturbance for cancer patients showed a significant relationship with Symptom Interference and cancer stage. The significant factors influencing Sleep Disturbance were Symptom Severity and Symptom Interference. They explained 40.5% of the variance in stage IV. Conclusion: Patients with cancer experienced Symptom Severity and Symptom Interference which led to a negative effect on Sleep Disturbance. The results suggest that intervention programs to reduce Symptom Severity, Symptom Interference could improve Sleep Disturbance for cancer patients.