Hollow fiber membranes (HFM) have been in use for many industrial and specialty applications. Although a great deal of research has been done in the past, the making of hallow fibers for a specified application is still an extremely difficult problem. Until now, the material formulation and the operating variables and conditions during spinning of fibers are specified more or less by trial-and-error method. In this study, the experimental design based on orthogonal array experimentation has been employed for discussing the relationship between the molecular weight cut-off (MWCO) and the dry-wet spinning conditions for making polysulfone hollow fibers for ultrafiltration. The factors considered in the experimental design included the contents of polysulfone (PSU) and poly(vinylpyrrolidone) (PVP) in the dope solution, the temperature of spinneret and the coagulation bath, the content of N-methyl-2-pyrrolidone (NMP) in bore liquid, the air gap length, and the relative humidity. The results indicate that the MWCO of the HFM was controlled by the PVP content and the temperature of the coagulation bath.