Cellulose (rayon) filaments were exposed to various concentrations of hydrochloric acid under aqueous and non-aqueous conditions in order to study differences in degradation. Two sources of polymeric diphenylmethane diisocyanate (pMDI) were used as non-aqueous media. As a consequence of the production process, pMDI was found to contain residual hydrochloric acid. Filament yarns were immersed for either 7 h or 7 d and purified to obtain pure filaments for further analysis. Single-filament tensile tests and molar mass measurements confirmed a significant degradation of the filament structure under non-aqueous conditions. Samples with the same amount of hydrochloric acid immersed in water, however, were rarely affected. Complementary X-ray diffraction indicated that the removal of the amorphous cellulose resulted in an increase in the cellulose crystallinity, which was manifested by a decrease in the width of the diffraction peaks. With this remarkable difference between aqueous and non-aqueous treatments, a quantitative proof to a new aspect about the processability of regenerated cellulose was presented. Amongst other fields of technical applications, these findings will have to be considered in composite engineering dealing with cellulosic fibre reinforcements. An effective way to avoid acidic hydrolysis was presented based on calcium carbonate as matrix filler.