Background: A cancer diagnosis has a significant impact and consequences for the patient and family. Cancer patients can develop a sense of hopelessness when distress becomes overwhelming and social support may be protective against hopelessness. Furthermore, among cancer survivors, optimism and hope have been linked to better adjustment and growth. Aim: The present study aimed to assess effect of anxiety, hope, and social support on quality of life of cancer patient undergoing chemotherapy. Subjects and Method: Design: Descriptive cross-sectional design was used. Setting: the study conducted in Oncology center in outpatients' clinics in Mogamaa-Elshefaa Hospital in Port Said city. Subjects: included a purposive sample of 155 cancer patients undergoing chemotherapy were included in the study. Tools: four tools used for data collection consisted of; The Hospital anxiety and depression scale, Adult Hope Scale, Multidimensional Perceived Social Support Scale, and WHO Quality of life scale (WHOQOL-BREF). The Results: 91% of the studied patients had high level of anxiety, 67.7% of cancer patients had high hope level. Also, 98.7% of them had high perceived social support levels, 85.8% had moderate level of QOL. Ther was statistically significant relation between level of anxiety, hope, and perceived QOL among cancer patients. Conclusion: Anxiety had a negative effect on QOL of cancer patients, while social support and hope had positive effect on them. Recommendations: Further research is necessary to design and implement educational programs for cancer patients and nurses regarding strategies of enhancing anxiety and its effect on cancer patients' levels of hope and QOL.