In this study, sulfur doped hexagonal boron nitride (S-h-BN) and fluorine doped hexagonal boron nitride (F-h-BN) were prepared via the exfoliation and heat treatment of bulk boron nitride (B-BN). Then, Human Serum Albumin (HSA) were immobilized onto the obtained hexagonal boron nitride nanolayer (NLs) surfaces to enhance irinotecan loading, which is a fluorescent molecule having excitation and emission at the wavelengths of 299 nm and 436 nm, respectively. The loading and release properties were studied at different pH values. Whereas the maximum loading amounts were achieved at the pH of 4.0 for all nanosheets, the pH value at which the maximum drug release was observed were found to be different for all samples. The physicochemical characterization of the nanosheets were conducted by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy methods. The XRD and FTIR results indicated the successful synthesis of h-BN and the 2D structure of the nanolayers were imaged using SEM and TEM methods. The F and S content inserted into the h-BN structure was determined to be about 2.45 and 0.1 at. % using the XPS method. In addition, the bonding structre of the modified h-BN monolayers were unraveled by the deconvulation of the XPS results.