Objective: To investigate the influence of neoadjuvant therapy on quality of life in patients with locally advanced mid/low rectal cancer before and after surgery. Methods: In 132 patients with locally advanced mid/low rectal cancer, 47 cases receiving preoperative neoadjuvant therapy were designated as observational group, and the remaining 85 cases who did not undergo preoperative neoadjuvant therapy were used as control group. The quality of life of the two groups was compared by the questionnaire scores of QLQ-C30 and QLQ-CR29 scale issued by European Organization for Research and Treatment of Cancer (EORTC). Results: Before operation, the scores for overall quality of life and emotional functioning in observational group were significantly lower than those in control group, while the scores for fatigue, nausea/vomiting, appetite loss, diarrhea, and financial problems as well as the scores for some symptoms that included hair loss, dry mouth, change of taste, and anxiety in observational group were significantly higher than those in control group (all P<0.05). Six months after operation, the scores for overall quality of life showed no statistical difference between the two groups (P=0.167), but the scores for pain, diarrhea, flatus or fecal incontinence, and burning skin pain in observational group were significantly higher than those in control group (all P<0.05), and moreover, the difference in diarrhea score persisted for up to 12 months after operation (P=0.023). The scores for impotence and dyspareunia were significantly higher and correspondingly, the score for sexual function was significantly lower in observational group than those in control group, which persisted from the preoperative stage to 12 months after operation (all P<0.05), however, the score for female sexual function in observation group was significantly lower than that in control group only in preoperative stage (P=0.017). Conclusion: Neoadjuvant therapy exerts a negative effect on the quality of life, especially the gastrointestinal and sexual function, in patients with locally advanced low rectal cancer.