Background: Caspase-3 is involved in the execution of apoptosis and is widely used as an apoptotic marker. Tumor necrosis factor-\alpha (TNF-\alpha) released from activated macrophages has various functions such as modulation of cell growth and differentiation, immunoregulation, coagulation, and regulation of endothelial cell function. This study investigated the immunohistochemical staining of caspase-3 and TNF-\alpha expression in the placentas of pregnant women with preterm premature rupture of membranes (PPROM). Methods: Placentas of 25 healthy, and 25 women with PPROM were processed for routine histological tissue processing. Placentas were stained with hematoxylin-eosin, caspase-3, and TNF-\alpha immunostaining. Results: Normal placental histology was observed in the control group. Amniotic epithelium, vascular structures, and fibrinoid accumulation were histologically normal. Leukocyte infiltration, thinned vessel walls with dilatation and congestion, syncytial nodes, and fibrinoid accumulation were increased in the PPROM group. The immune activity of caspase-3 expression was mainly negative in placental components such as syncytial nodes, vascular endothelium, fibrinoid accumulation, and macrophages in the control group. In the PPROM group, caspase-3 positive reaction was increased in the amniotic membrane and epithelium, endothelial cells, fibrinoid accumulation, and areas of inflammatory cell infiltration. In the control group, negative TNF-\alpha expression was observed in the placental membranes and structures. In the PPROM group, TNF-\alpha expression was increased in inflammatory cells, endothelial cells, and syncytial nodes. Conclusions: Placentas of patients with PPROM showed loss and weakened membranes with increased placental pathology, and increased expression of caspase-3 and TNF-\alpha. We suggest that caspase-3 and TNF-\alpha signaling pathways can be used as a marker in the progression of PPROM.