The popularity of lithium-ion (Li-ion) batteries has increased over the recent years. Because of the strong dependence of the Li-ion battery operation characteristics on temperature, heat generation in the battery has to be taken into account. The entropy change of a Li-ion battery has a significant influence on heat generation, especially at a low C-rate current. Therefore, it is necessary to consider the entropy change profile in the estimation of heat generation. In the paper, a method to determine the entropy change (ΔS) profile by heat flux measurements of a cylindrical Li-ion cell is proposed. The method allows simultaneous measurements of the thermal diffusivity and ΔS of the cylindrical cell. The thermal diffusivity and ΔS measurements are carried out by a gradient heat flux sensor (GHFS). The comparison between the ΔS profile determined by the GHFS method with that obtained using a standard potentiometric method clearly shows that the entropy change measurements could be made by using a GHFS. Even though the uncertainty of the reported method is higher than that of the potentiometric method, a significant decrease in the experiment time compared with the potentiometric method is a major advantage of this method.