Chemotherapy as a cornerstone of cancer treatment is slowly being edged aside owing to its severe side effects and systemic toxicity. In this case, nanomedicine has emerged as an effective tool to address these drawbacks. Herein, a biocompatible carrier based on bovine serum albumin (BSA) coated gadolinium oxide nanoparticles (GdO@BSA) was fabricated for curcumin (CUR) delivery and its physicochemical features along with its potential anticancer activity against nasal squamous cell carcinoma were also investigated. It was found that the fabricated GdO@BSA containing CUR (GdO@BSA-CUR) had spherical morphology with hydrodynamic size of nearly 26 nm, zeta-potential of -36 mV and high drug (CUR) loading capacity. Drug release profile disclosed that the release of CUR from the prepared GdO@BSA-CUR nanoparticles occurred in a sustained- and pH-dependent manner. Also, in vitro cytotoxicity analysis revealed that the fabricated GdO@BSA nanoparticles possessed excellent biosafety toward HFF2 normal cells, while GdO@BSA-CUR appeared to display the greatest anticancer potential against RPMI 2650 and CNE-1 cancer cell lines. The results also show that the GdO@BSA nanoparticles were compatible with the blood cells with minor hemolytic effect (< 3%). The manufactured NPs were found to be completely safe for biological applications in an in vivo subacute toxicity study. Taken together, these finding substantiate the potential anticancer activity of GdO@BSA-CUR nanoparticles against nasal squamous cell carcinoma, but the results obtained demand further studies to assess their full potential.