Temperature-responsive polymers with a lower critical solution temperature (LCST) have attracted much attention in biomedical and biotechnological fields. It is important to tune their cloud point temperature (Tc) in a broad temperature range as desired by the applications. In this study, new thermo-responsive 2-hydroxy-3-isopropoxypropyl starches (HIPS) was synthesized using Hylon V starch as raw material and isopropyl glycidyl ether as hydrophobic reagent. The phase transition behavior of HIPS and their Tc were determined by spectrophotometry. The effects of several conditions on the Tc of the HIPS were also investigated, which indicated that varying the molar substitution (MS) of HIPS can adjust Tc in a broad temperature range from 69 to 28 °C by changing the hydrophobic-hydrophilic balance of starch. The phase transition became fast and the Tc decreased with increasing polymer concentration. The effect of a series of sodium salts on the Tc of aqueous HIPS solutions was reported and the effectiveness of ions follows a trend, known as Hofmeister series. Several organic solvents were selected and the organic additives with small molecular weight can also regulate the Tc of HIPS in a certain range by changing the polymer-water interactions.