The (2-hydroxypropyl)cellulose (HPC) derivatives can be regarded as a system which is composed of poly(saccharide) main chain (hydrophilic segment) and aliphatic side chain as a hydrophobic (lipophilic) segment of the macromolecules. The influence of the hydrophobic effect on the thermotropic mesomorphism of HPC derivatives was investigated. The correlation between d-spacing of HPC-derivatives estimated from X-ray measurements and hydrophobic effect of the side chain was found. The relative hydrophobicity variation of the side chains of HPC-derivatives leads to an increase in the d-spacing between poly(saccharide) main chains. On the other hand, the increasing d-spacing in the HPC-derivatives shifts their transition temperatures to isotropic state and glass transition temperatures towards lower temperature range. It was suggested that the property/structure correlation of the HPC-derivatives is affected by the balance between hydrophilic and hydrophobic parts of the HPC-derivative macromolecules.