PROM is one of the common complications of perinatal period, which seriously threatens the mother and newborn. The purpose of this study was to identify the role of NLRC4 inflammasomes in this process and their underlying mechanisms. We performed high-throughput RNA sequencing of fetal membrane tissue from 3 normal pregnant women and 3 term-premature rupture of fetal membrane (TPROM) patients who met the inclusion criteria, and found that NLRC4 was significantly up-regulated in TPROM patients. An observational study of TPROM patients (PROM group, n = 30) and normal pregnant women (control group, n = 30) was performed at the Xuzhou Maternal and Child Health Hospital affiliated to Xuzhou Medical University from May 2018 to May 2019. The expression of genes involved in inflammasome complex including NLRC1, NLRC3, AIM2, NLRC4, ASC, caspase-1, IL-6, IL-18 and IL-1βwas determined via real-time PCR, immunohistochemistry and immunofluorescence. Measurement of NLRC4 level in serum was conducted by ELISA assay. The results showed that the NLRC4, ASC, caspase-1, IL-1β and IL-18 levels in fetal membrane, placental tissues and maternal serum were markedly higher in the PROM group than that in the control group. In conclusion, NLRC4 is a markedly up-regulated gene in TPROM fetal membrane tissue, suggesting that NLRC4 is involved in the occurrence and development of TPROM; NLRC4 levels in maternal blood serum are closely related to TPROM and have the potential to assist doctors in predicting and diagnosing PROM.