Along with the increased usage of cellulose in the manufacture of novel materials, those of its derivatives that have good solubility in water or organic solvents have become increasingly important. In this study, hydroxypropyl cellulose (HPC), a cellulosic derivative with distinct features, was utilized to investigate how two of the most-selective oxidation methods currently available in the literature act on the constituent OH groups of both the side chain and the anhydroglycosidic unit in HPC. The oxidation reactions were carried out first using TEMPO, sodium hypochlorite, and sodium bromide, then sodium periodate (NaIO4), for 5 h. A combination of these two protocols was applied. The amount of aldehyde and number of carboxylic groups introduced after oxidation was determined, while the changes in the morphological features of oxidized HPC were, additionally, assessed. Furthermore, utilizing Fourier-transform infrared spectra, X-ray diffraction, and thermogravimetric studies, the chemical structure, crystallinity, and thermal stability of the oxidized HPC samples were examined and compared.