Background: Ovarian cancer is the most lethal gynecologic malignancy. Nearly 75% of patients were diagnosed at advanced stages. Despite 60%-80% of patients achieve complete remission after treatment with surgery combined with chemotherapy, about 60% of patients relapse within two years, more than 50% of patients develop chemotherapy tolerance with only 30% five-year survival rate. Platinum resistance-induced recurrence and platinum intolerance result in poor prognosis. Thus, there is an unmet need for innovative therapy of advanced ovarian cancer. We have developed a novel non-genetically modified ex vivo-expanded allogeneic NK cells from peripheral blood (PB). The expanded PB-NK cells have highly cytolytic activity and have the capacity to preferentially reside in ovary. We conducted a phase I clinical trial for evaluation of safety and efficacy of allogeneic NK cells in treatment of patients with refractory or recurrent ovarian cancers. Methods: Patients with advanced ovarian cancer who failed after multiline treatment were enrolled and received the treatment with allogeneic NK cells. The treatment was divided into low, medium and high dose groups with a 28-day cycle. safety and efficacy were evaluated after receiving two cycles of allogeneic NK cell infusion. Results: A total of 4 patients with advanced ovarian cancer who failed multiline therapy completed two courses of cell infusion therapy and evaluation. The median age of patients was 58 years (range 50 to 71 years). The median number of lines of treatment was 6 (range 3-7). One recurrent patient with platinum intolerance received low dose of NK cells and three relapse or refractory patients with platinum resistance received medium dose of allogeneic NK cell therapy. The patient in low-dose group and one patient in medium-dose group were evaluated for stable disease (SD), the other two patients in medium-dose group were disease progression after two courses of treatment. Notable, the patient in low-dose group continued to receive treatment with the same dose and achieved partial response (PR) after three courses of treatment. Upon receiving continuous NK cell therapy, the tumor lesions continued to shrink, with the best result was 60% reduction. It was re-evaluated as progressive disease (PD) 6 months after treatment was discontinued. Adverse events during the follow-up period included grade I fever in 4 (100%), grade I drowsiness in 1 (25%), grade I chills in 1 (25%), and grade I malaise in 1 (25%). No CRS or GVHD occurred. Conclusions: We report the safety and efficacy of allogeneic PB-NK cells in treatment of relapse or refractory ovarian cancer. The results showed that the allogeneic PB-NK cells are safe and feasible for the treatment of ovarian cancer, indicating a promising curative effect. There is no host versus graft reaction upon receiving continuous allogeneic NK cell therapy. Clinical trial information: NCT03619954.