In order to develop advanced hemodiafiltration membrane with favorable biocompatibility and efficient dialysis performance, novel thin film nanofibrous composite (TFNC) ultrafiltration (UF) membranes consisting of sulfonated poly(vinyl alcohol) (s-PVA) blended PVA hydrogel barrier layer and electrospun polyacrlonitrile (PAN) nanofibrous supporting layer were designed and fabricated by combining electrospinning and conventional surface coating techniques. The mesh sizes of hydrogel network of s-PVA/PVA barrier layer could be tuned by varying the blending content of s-PVA. The optimized s-PVA/PVA TFNC UF membrane (S-P-TFNC-1-3) possessed high pure water flux up to 380 Lm(-2) h(-1) bar(-1) with high bovine serum albumin (BSA) rejection (> 90%). Besides, the introduction of s-PVA into the hydrogel barrier layer endowed the TFNC membranes with enhanced hydrophilicity, antifouling property and biocompatibility (decreased protein adsorption, prolonged clotting time, suppressed platelet adhesion, lower hemolysis ratio and more benefits for cell proliferation) due to the presence of sulfonic groups. The dialysis simulation experiment results of S-P-TFNC-1-3 showed that 84.2% of urea and 60.9% of lysozyme were cleaned and over 95% of BSA was retained after 4 h dialysis process. Especially, the removal of middle-molecule uremic toxin was more efficient than conventional hemodialysis membranes reported so far, and high retention of big proteins was achieved simultaneously. This work exposes a window of opportunity for modified PVA TFNC membranes in blood purification applications.