Objective To investigate the quality of life upon discharge and its relationship with prognosis in the elderly patients undergoing surgery for primary colorectal cancer (CRC). Methods A total of 250 elderly patients surgically treated for primary CRC from January 2017 to January 2020 in the First Affiliated Hospital of Hainan Medical University were enrolled as the study subjects, and 10 cases were excluded. Upon discharge, the quality of life of patients was evaluated using the specific scale for quality of life of cancer patients. The 240 patients were divided into high life quality group (n=94) and low life quality group (n=146) based on quality of life scores. SPSS statistics 20.0 was used for data analysis. t test or chi-square test was used for data comparison between two groups. Binary logistic regression model was used to analyze the factors affecting postoperative quality of life in the elderly CRC patients. Pearson linear correlation analysis was performed to analyze the correlation between the quality of life upon discharge and survival time in the elderly CRC patients. Results The overall quality of life of elderly patients surgically treated for CRC upon discharge was at a moderate level. Kaplan-Meier curve after 3 years of follow-up found that the survival status of the patients in the good life quality group at 3 years after surgery was better than that in the poor life quality group (Rank=4.708, P=0.030). Pearson linear correlation analysis suggested that the dimensions of physical function, psychological function, and symptom/side effects were positively correlated with the survival time of patients (r=0.327,0.241,0.311; P<0.05). Binary logistic regression analysis showed that the self-rated economic burden caused by disease (OR=2.396,95%CI 1.240-4.630), self-rated sleep quality (OR=2.077,95%CI 1.250-3.451), malnutrition (OR=1.404,95%CI 1.099-1.793), Eastern Cooperative Oncology Group (ECOG) grading (OR=1.547,95%CI 1.017-2.352), and tumor metastasis (OR=1.818,95%CI 1.127-2.934) were independent factors affecting the quality of life, and that education (OR=0.556,95%CI 0.407-0.759) and social support (OR=0.527,95%CI 0.320-0.867) were protective factors for the quality of life. Conclusion The quality of life of the elderly CRC patients upon discharge is at a moderate level, and the quality of life upon discharge has a certain impact on the long-term prognosis of patients. Actively improving the sleep quality during hospitalization, strengthening the nutritional support and social support, and enhancing the quality of life during hospitalization are of some significance in improving the prognosis of the patients.