Kruppel-like factor 4 (Klf4) is a zinc finger transcriptionfactor and plays crucial roles in Xenopus embryogenesis. However, its regulation during embryogenesis is stillunclear. Here, we report that Tcf7l1, a key downstream transducerof the Wnt signaling pathway, could promote Klf4 transcription and stimulate Klf4 promoter activity in early Xenopus embryos. Furthermore, cycloheximide treatmentshowed a direct effect on Klf4 transcriptionfacilitated by Tcf7l1. Moreover, the dominant negative form of Tcf7l1(dnTcf7l1), which lacks N-terminusof the β-catenin binding motif, could still activate Klf4 transcription, suggesting that thisregulation is Wnt/β-catenin independent. Taken together, ourresults demonstrate that Tcf7l1 lies upstream of Klf4 to maintainits expression level during Xenopus embryogenesis.