Objective To explore the possible mechanism of the interaction between microRNA-142-3p (miR-142-3p) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on cytokines during unexplained recurrent spontaneous abortion (URSA). Methods 45 female patients with URSA who were admitted to University of Chinese Academy of Sciences Shenzhen Hospital(Guangming) from September 2016 to December 2017 were selected as the abortion group, and 40 healthy early pregnant women who were examined in this hospital at the same time were selected as the control group for a retrospective study. The ratio of CD4+ CD25+ Treg cells in peripheral blood of each group was detected by flow cytometry, and the expression levels of Th1 and Th2 cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Results The percentage of CD4+ CD25+ Treg cells in the control group was higher than that in the abortion group (P<0.05). Compared with the control group, the expression levels of interleukin-10(IL-10) and interleukin-4(IL-4) in peripheral blood of the abortion group were significantly decreased, while the expression levels of interleukin-2(IL-2) and interferon-γ (IFN-γ) were significantly increased (P<0.05). Meanwhile, the ratios of IL-2/IL-10 and IFN-γ/IL-4 in the abortion group were higher than those in the control group (P<0.05). Detection of luciferase reporter gene showed that miR-142-3p had strong binding ability to CTLA-4. Conclusion miR-142-3p has a potential inhibitory effect on the expression of CTLA-4, which may be one of the possible mechanisms to promote URSA.