Objective: To screen the differently expressed miRNAs study the expression andfunction of let-7f-5p in unexplained recurrent spontaneous abortion (URSA) and investigate the roles of miRNAs played in URSA. Methods: The miRNA-sequencing was applied to screen miRNAs that differently expressed in URSA placental villous; The qRT-PCR was used to validate the miRNA’s expression of screened miRNAs; The DAVID was applied to analyze pathway; The qRT-PCR was conducted to measure the expression of target genes in p53 pathway. Results: The expression of let-7f-5p was markedly up-regulatedhighly expressed in URSA placental villous; The targets of let-7f-5p were abundant in p53 pathway, and the expression of MDM-X and MDM2 was significantly down-regulated, while the expression of p53 was significantly up-regulated. Conclusion: let-7f-5p might promote cell apoptosis in URSA by regulating the expression of MDM-X/MDM2/p53 in p53 pathway.