In this work, poly(vinyl chloride) (PVC)/CuO-VB1(vitamin B-1) nanocomposite (NC) films were prepared by solution casting method. For this purpose, CuO nanoparticles (NPs) were chosen as an appropriate nano-filer to incorporate into the PVC matrix. To prevent aggregation and make NPs more compatible with the polymer matrix, surface modification of NPs was performed. Thiamine (vitamin B-1) is a biological molecule used as a bio-safe modifier. Then, PVC/CuO-VB1 NCs were obtained by addition of different weight percentages (3, 5, and 7 wt%) of modified NPs into the PVC matrix under ultrasonic irradiation. The prepared NCs were examined using various techniques. The results confirmed that relative changes in the obtained data and morphology, as the concentration of nano-filler was increased. Furthermore, incorporating the NPs into PVC caused an increase in thermal stability of NCs as compared to neat PVC. FE-SEM and TEM morphological analysis showed good compatibility of modified CuO with the PVC matrix. The contact angle results verified that hydrophilicity of NCs increased by adding fillers into the polymer matrix. Finally, addition of NPs into the PVC matrix had influenced on optical absorption and mechanical behaviors of PVC.