Hydroxypropyl cellulose (HPC) is a nonionic, thermo-responsive polymer with temperature-dependent phase behavior. This behavior can be modified by grafting molecular units and polymer brushes onto the cellulose backbone. However, the thermo-response of such modified celluloses under biological and environmental conditions, such as pH, has been scarcely reported. This study details the synthesis and characterization of dual-temperature- and pH-responsive poly(vinyl pyrrolidone)-graft-hydroxypropyl cellulose (PVP-g-HPC) by organocatalyzed visible-light-driven atom transfer radical polymerization (O-ATRP). Employing a "grafting-from" approach, we synthesized a series of PVP-g-HPCs with controlled molecular weight and narrow dispersity. By precisely adjusting the molar ratios of HPC and N-vinyl pyrrolidone, we investigated the changes in the lower critical solution temperature (LCST) under various pH conditions. Our results revealed that the thermo-responsive PVP side chains exhibited a reverse dependence on pH. Additionally, the LCST window of HPC thermo-responsive derivatives was expanded to 37 °C within the physiological pH range.