Objective To investigate the zinc finger protein A20 (also known as tumor necrosis factor-induced protein 3) in placenta and correlation between TNFAIP3 expression level and neonatal weight and placental weight in Low birth weight babies (LBW) and its role in the pathogenesis of LBW. Method Thirty pregnant women with low birth weight babies (LBW) who delivered in Gansu Provincial Maternal and Child Health Hospital from September 2021 to May 2022 were selected. 30 healthy pregnant women who delivered during the same period were selected as normal pregnancy (NP). qRT-PCR and Western blot were used to detect the expression of A20 in placental tissues of the two groups. The immunohistochemistry was used to detect the expression level of A20 in placental tissues. The correlation between the expression level of A20 and neonatal weight and placental weight in LBW group was analyzed. At the same time, human placental trophoblast cells (HTR-8/SVneo) were cultured in vitro and divided into control group (NC) and LPS group (100ng/mL). After overexpression of adenovirus A20 gene, the expressions of A20 protein, NF-κB binding protein p65, p-p65, TNF-α and IL-1β in placental trophoblast cells were detected by Western blot. The expressions of TNF-α and IL-1β in supernatant were detected by ELISA. Results Compared with the NP group, there were no significant differences in age and gestational age (P＞0.05), but there were significant differences in neonatal weight, placental weight and Apgar score at 1min and 5min (P＜0.05)The expression of A20 was significantly lower in LWB group (P＜0.01) Immunohistochemistry showed that A20 was decreased in placental tissue of LBW group, and it was positively correlated with neonatal weight and placental weight (P＜0.05) In addition, compared with NC group, the protein expression of A20 in LPS group was significantly decreased (P＜0.05), while the protein expression of P-p65, TNF-α and IL-1β in LPS alone group was significantly decreased (P＜0.05) After overexpression of A20 gene, the expression of A20 was increased (P＜0.05), while the expression of P-p65, TNF-α and IL-1β were decreased (P＜0.05) Conclusion A20 is closely related to the occurrence and development of LBW, and its overexpression can effectively inhibit the production of inflammatory cytokines in trophoblast cells induced by LPS, which is expected to be a molecular marker and therapeutic target for predicting LWB