Membrane structure design is critical for the development of high-performance hemodialysis membranes. Here, a thin-film nanofibrous composite (TFNC) membrane, consisting of a two-tier composite structure, i.e., an ultrathin hydrophilic separation layer of chemically cross-linked polyvinyl alcohol (PVA), and an electrospun polyacrylonitrile (PAN) nanofibrous supporting layer, was demonstrated as the hemodialysis membrane for the first time. The optimized PVA/PAN TFNC membrane exhibited high permeability (similar to 290.5 L/m(2)h at 0.1 MPa) and excellent selectivity which should be attributed to its unique structure with ultrathin separation layer and highly porous supporting layer. In addition, the TFNC membrane also possessed excellent overall mechanical properties, good hydrophilicity and comparable hemocompatibility properties (protein adsorption, platelet adhesion, complement activation, hemolysis ratio). The hemodialysis simulation experiments on optimized TFNC membrane showed that 82.6% of urea and 45.8% of lysozyme were cleaned and 98.8% of bovine serum albumin (BSA) was retained. The TFNC membranes exhibited excellent hemodialysis performances, especially for the middle-molecule uremic toxin removal, which was more efficient than conventional hemodialysis membranes reported so far, suggesting PVA/PAN TFNC membranes as promising alternatives for hemodialysis applications.