To explore the possible significance of the expressions of FGF21, β-arrestin1, and p53/MDM21 in the occurrence of missed abortion of women during the first trimester of pregnancy. Methods: A total of 53 women with missed abortion during their first pregnancy were selected in study group and 53 healthy women with induced abortion were selected in control group from January 2018 to August 2019. The expressions of FGF21, β-arrestin1, p53, and MDM21 in villus tissues of the women in the two groups were analyzed by polymerase chain reaction and Western Blot. The relationship between the expressions of FGF21, β-arrestin1, p53, and MDM21 in villus tissues of the women and their missed abortion occurrence was analyzed by Spearman correlation analysis. Results: The bleeding time, the menstrual revulsion time, and the blood loss of the women in the study group were significantly higher than those of the women in the control group, but the endometrial thickness of the women in the study group was significantly lower (P<0.05). The expressions of P53 (1.394±0.12) and MDM2 (1.581±0.16) in villus tissues of the women in the study group were significantly higher than those (0.485±0.09 and 0.285±0.05) of the women in the control group. The expressions of β-arrestin1 (0.738±0.15) and FGF21 mRNA (0.413±0.18) in villus tissues of the women in the study group were significantly lower than those (1.613±0.19 and 1.288±0.29) of the women in the control group (all P<0.01). In the study group, the expressions of p53 and MDM2 in villus tissues of the women was negatively correlated with their expressions of β-arrestin1 and FGF21 in villus tissues (all P=0.000). During the occurrence of missed abortion of women during the first trimester of pregnancy, the high consumption of β-arrestin1 may inhibit angiogenesis and increase apoptosis by p53/MDM2 signaling pathway, thus promoting the occurrence of missed abortion. FGF21 may play some certain role in inhibiting missed abortion during the first trimester of pregnancy.