Objective To explore the express of formyl peptide receptor 2(FPR2) in villi of recurrent spontaneous abortion ( RSA) , the effect on proliferation, migration and invasion of trophoblast, and the mechanism to clarify the effect of FPR2 on trophoblast function and explore its role and mechanism in recurrent spontaneous abortion. Methods Clinical villus specimens of 30 nonnal and 30 RSA patients were collected. Immunohistochemical staining, Real-time PCR and Western blotting were used to detect the location and expression of FPR2 in villi of patients with RSA and nonnal pregnant women. CRISPR/Cas-9 technique was used to knock down FPR2 in HTR-8/SVneo cells, CCK-8 assay, wound healing and Transwell assays were used to detennine the ability of cell viability, migration and invasion. Immunofluorescent staining and Western blotting were used to analyze the changes of phosphorylated p38 MAPK ( p-p38 MAPK)/p38 MAPK protein expression after applying with p38 MAPK inhibitor SB203580 alone or in combination. Results The expression of FPR2 in villi of patients with RSA increased. FPR2 knock-down improved the biological functions of HTR-8/Svneo cells such as proliferation, migration and invasion significantly. The expression of p-p38 MAPK was up-regulated significantly by FPR2 knock-down, and the ability enhancement of migration and invasion of trophoblasts was reversed partially by SB203580 which inhibits p38 MAPK pathway. FPR2 knock-down caused the change of p38 MAPK signaling pathway related to proteins. Conclusion FPR2 is highly expressed in trophoblasts of RSA patients, and inhibits the migration and invasion of trophoblasts through p38 MAPK signaling pathway, which ma)' play an important role in RSA.