Objective To analyze the application effect of targeted nursing in hemodialysis patients with skin swelling at puncture site. Methods A total of 70 patients with diabetic nephropathy who underwent hemodialysis and had redness and swelling at the puncture site in our hospital from January to December 2021 were selected as subjects. They were divided into control group and observation group by random number table method, with 35 cases in each group. The control group was given routine nursing, and the observation group was given targeted nursing. The nursing effect, clinical related indicators and nursing satisfaction of the two groups were compared. Results The total effective rate of nursing in the observation group was 97.14%, which was higher than 74.29% in the control group (P<0.05). The disappearance time of swelling in the observation group was earlier than that in the control group, and the VAS score was lower than that in the control group (P<0.05). The nursing satisfaction of the observation group was 97.14%, which was higher than 77.14% of the control group (P<0.05). Conclusion Targeted nursing intervention is effective in the treatment of redness and swelling at the puncture site by dialysis, which can shorten the duration of redness and swelling, relieve pain, and has high patient satisfaction. It is worthy of clinical application.