Background: This study explores the efficacy of combining recombinant human interferon α-2b with the cervical loop electrosurgical excision procedure (LEEP) in the treatment of cervical precancerous lesions. Methods: Clinical data from 100 patients treated for cervical precancerous lesions at our hospital from January 2021 to January 2023 were retrospectively analyzed. Patients were divided into two groups based on treatment method: an experimental group (50 cases) and a control group (50 cases). The control group received LEEP using a high-frequency electric knife, while the experimental group was treated with LEEP combined with recombinant human interferon α-2b gel. The differences in efficacy between the two groups were compared. Results: The experimental group demonstrated a significantly higher overall effective rate compared to the control group (p < 0.05). There was no significant difference in the incidence of surgical complications between the two groups (p > 0.05). At 6 months and 1 year after surgery, the experimental group exhibited a lower recurrence rate and a higher clearance rate of high-risk human papillomavirus (HR-HPV) compared to the control group (p < 0.05). Three months after treatment, the scores for environment, social relationships, physiology and psychology in the experimental group were significantly higher than those in the control group (p < 0.001). Conclusions: Combining LEEP with recombinant human interferon α-2b in patients with cervical precancerous lesions effectively eliminates HPV, improves quality of life, reduces complications and recurrence and is safe for medication.