A composite consisting of mechanically strong Poly(vinylidene fluoride) (PVDF) and biochemically favorable Cellulose acetate (CA) nanofibers can be considered as an excellent choice due to their excellent mechanical properties of PVDF and desirable biological properties of CA. However, preparing nanofibers of composites, involving CA requires the use of harsh acidic solutions and high temperatures, which can have serious consequences on a bio‐aspect of CA. In this study, we have successfully prepared suitable solutions comprising of PVDF and CA in dimethylformamide. Subsequently, these solutions were directly ejected out as nanofibers during the process of electrospinning. The nanofibers synthesized were characterized for physicochemical properties by scanning electron microscopy, contact angle, Fourier transform infrared, thermogravimetric, and X‐ray diffraction spectroscopy. The results revealed that CA can be easily introduced in PVDF nanofibers, using a single solvent (i.e., dimethylformamide). The introduced strategy can favorably preserve the inherent biological nature of CA. Moreover, the nanofibers prepared using this methodology was investigated for cell toxicity and cell attachment properties. These studies were carried to figure out the beneficial features shown by the CA to suppress inherent toxicity of PVDF nanofibers. The results of these studies proved that NIH 3T3 fibroblasts upon incubation in the presence of composite nanofibers containing CA can proliferate well when compared to pristine PVDF nanofibers. POLYM. COMPOS., 40:1619–1630, 2019. © 2018 Society of Plastics Engineers