Objective To explore the effect of comprehensive intervention on postoperative pain of patients with rectal disease. Methods A total of 200 patients with postoperative pain after the treatment of anorectal perianal disease from May 2015 to May 2016 were randomly divided into two groups with 100 cases each. The control group was treated with drugs and usual nursing, the observation group were adopted drugs and comprehensive nursing intervention. The improvement of pain, psychological states and the quality of sleep were compared between two groups. Results The VAS pain scores at 4, 6, 12, 24, 48 h after treatment was (2.1 ± 0.6), (3.3 ± 0.4), (3.5 ± 0.3), (2.3 ± 0.5), (1.9 ± 0.5) points in the observation group, and (3.0 ± 0.5), (5.1 ± 0.6), (6.2 ± 0.6), (5.7 ± 0.8), (5.8 ± 0.5) points in the control group, and the difference was statistically significant (t=8.539-38.806, P < 0.05). The Self-rating Anxiety Scale was (20.32 ± 6.16) points in the observation group, and (35.58 ± 7.43) points in the control group, and the difference was statistically significant (t=41.188, P<0.05). The sleep quality, the amount of sleep , sleep time, sleep efficiency of Pittsburgh Sleep Quality Index Questionnaire scores was (0.91±0.28), (0.86±0.2), (0.83±0.27), (0.59±0.31), (0.62±0.27), (0.58±0.41), (4.39±1.79) points in the observation group, and (1.61± 0.88), (1.32 ± 0.75), (1.59 ± 0.89), (1.34 ± 0.58), (1.36 ± 0.45), (1.29 ± 0.86), (8.51 ± 3.55) points in the control group, and the difference was statistically significant (t=4.557-17.740, all P<0.05). Conclusions The comprehensive intervention on postoperative pain relief in patients with anal disease is significant, it is beneficial to relieve the pain response, improve sleep quality, and achieve physical and psychological comfort, and has a positive effect to clinical.