Objective To explore the application effect of cluster nursing intervention in the treatment of Ⅱ-Ⅳstage mixed hemorrhoids patients with internal hemorrhoids ligation. Methods A total of 82 patients with stage Ⅱ-Ⅳmixed hemorrhoids in our hospital were treated with internal hemorrhoids ligation. The patients were divided into two groups by red blue double color ball method, 41 cases in each group. The patients in the control group were given routine nursing. The observation group was given cluster nursing intervention on the basis of the control group. The postoperative pain of the patients in the two groups was compared, and the quality of life before and after nursing was evaluated.The complications were observed. Results There was no significant difference between the pain score postoperative 6 h was (3.54±0.52) points of the observation group and the control group of (3.61±0.55) points (P＞0.05); the pain score postoperative 12 h was (2.68±0.51) points, the pain score postoperative 24 h was (1.84±0.41) points and the pain score postoperative 48 h was (1.09±.27) points of the observation group were lower than those of the control group in the above period of (3.23±0.48), (2.38±0.49), (1.52±0.31) points, the differences were statistically significant (P<0.05).There was no significant difference in the quality of life score of the observation group before nursing of (62.31±7.92)points compared with that of the control group of (62.58±7.16) points (P＞0.05); the quality of life score of the observation group after nursing was (76.53±8.39) points, was higher than that of the control group of (69.62±7.47) points, and the difference was statistically significant (P<0.05). The total incidence of complications in the observation group(7.32%) was lower than that of the control group (24.39%), the difference was statistically significant (P<0.05). Conclusion The effect of cluster nursing intervention in the treatment of Ⅱ-Ⅳstage mixed hemorrhoids patients with internal hemorrhoids ligation is definite.