Cues of maternal and paternal origins interact to control seed development, and the underlying molecular mechanisms are still far from clear. Here, we show thatTOPOISOMERASE Iα(TOP1α),UP-FRAMESHIFT SUPPRESSOR 1(UPF1), andTRANSPARENT TESTA GLABRA2(TTG2) gametophytically, biparentally regulate seed size inArabidopsis.TOP1αandUPF1are mainly expressed in antipodal cells, and loss of their function leads to ectopicTTG2expression in these female gametophytic cells. We further demonstrate that TOP1α and UPF1 directly repressTTG2expression through affecting its chromatin status and determine its relative expression in antipodal cells versus sperm cells, which controls seed size in a dosage-dependent and parent-of-origin-dependent manner. The molecular interplay among these three genes explains their biparental gametophytic effect during diploidy and interploidy reciprocal crosses. Taken together, our findings reveal a molecular framework of parental interaction for seed size control.