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Introduction Cervical cancer screening is difficult to initiate and sustain during war due to disrupted health services, population displacement and limited clinical capacity. Evidence on whether human papillomavirus (HPV)-based screening using self-sampling can function as a screening pathway during armed conflict is unknown. This study evaluated the feasibility, acceptability and operational performance of HPV self-sampling for cervical cancer screening in a war-affected region of Ukraine.Methods Women aged 30–60 years living in Zaporizhzhia Oblast, Ukraine, were offered HPV testing using self-collected cervicovaginal samples distributed through outpatient clinics, community outreach activities and refugee centres. Samples were analysed locally using PCR-based HPV assays with external laboratory quality assurance. Women positive for HPV16/18 were referred directly for colposcopic evaluation. Primary outcomes included screening uptake, kit return rate, HPV positivity and follow-up completion among HPV16/18-positive women. Secondary outcomes included turnaround times, HPV positivity by age and sampling setting, and participant feedback.Results Between April and December 2025, 593 women were offered HPV self-sampling; only 4 (0.67%) declined participation. Of 589 distributed kits, 572 samples were returned and analysed (attendance rate 96.46%, 572/596), with non-return occurring only in refugee centres. Overall, 52/572 women (9.1%) tested positive for targeted HPV types, including 22 (3.8%) positive for HPV16/18 and 30 (5.2%) positive for HPV31/33/35/45/52/58. All women testing positive for HPV16/18 were contacted and referred for specialist follow-up; among those completing follow-up, all were assessed within 2 months. Median turnaround time from self-sampling to results was 6.3 days. All recorded participant feedback was positive.Conclusion HPV self-sampling-based cervical cancer screening can be initiated and maintained during active war with high uptake, timely laboratory processing and effective referral of women at highest risk. Simplified, low-contact screening pathways may support cervical cancer prevention under wartime conditions.Trial registration number NCT07275333.