Objective To observe the efficacy and safety of targeted nursing in the treatment of keloid with CO2 fractional laser combined with drug introduction. Methods A total of 110 patients with keloid admitted to our hospital from February 2019 to October 2020 were selected as the research objects. Fifty-five patients who were treated from Februaryto December 2019 and supplemented with routine nursing were included in the control group. Fifty-five patients who were treated from January to October 2020 and supplemented with targeted nursing were included in the observation group. Both groups were treated with CO2 fractional laser combined with drug introduction. The adverse mood (SDS, SAS) scores, incidence of adverse reactions, recurrence rate and patient satisfaction were compared between the two groups. Results The scores of SDS and SAS in the observation group were lower than those in the control group (P <0.05). The incidence of adverse reactions and recurrence rate in the observation group were lower than those in the control group (P <0.05). The satisfaction of patients in the observation group was higher than that in the control group (P <0.05). Conclusion The effect of CO2 fractional laser combined with drug introduction in the treatment of keloid patients is ideal. The treatment combined with targeted nursing intervention measures can improve the patients' bad mood, reduce the incidence of adverse reactions, reduce the recurrence rate, and have high patient satisfaction, which is worthy of clinical application.