Human papillomavirus (HPV) infection is the source of plantar warts, a common dermatological disorder. Topical medications paired with needling are only a few of the therapy techniques that have been used. In this investigation, the effectiveness of topical 5% fluorouracil (5-FU) with needling and 30% trichloroacetic acid (TCA) with needling in the treatment of plantar warts was investigated. Methods: The topical application of either 5% 5-FU with needling (Group A) or 30% TCA with needling (Group B) was given to a total of 60 patients with plantar warts. At baseline, 4, 8, and 12 weeks, wart clearance rates and wart size reduction were evaluated. Additionally, adverse occurrences were noted. Results: Compared to Group B (68.3%), Group A had a significantly greater wart clearance rate at 12 weeks (82.5%) (p=0.032). At all time intervals, Group A had a larger decrease in wart size compared to Group B (p <0.05). Between the two groups, there were few and comparable adverse effects. Conclusion: According to current research, the treatment of plantar warts with topical 5% 5-FU and needling is superior to topical 30% TCA and needling. Higher wart clearance rates and larger wart size reduction were the outcomes of this treatment approach. It is need to conduct more research to verify these conclusions and assess long-term effects