The relationship between retention behavior of eight 1,2-O-cyclohexylidene xylofuranose derivatives and their molecular characteristics was studied using chemometric Quantitative Structure-Retention Relationships (QSRR) approach. QSRR analysis was carried out on the retention parameter RM0, obtained by normal-phase thin-layer chromatography, by using molecular descriptors, as well as partition coefficient for n-octanol/water bi-phase system (logP). Molecular descriptors were calculated from the optimized structures. Principal component analysis (PCA) followed by hierarchical cluster analysis (HCA) and multiple linear regression (MLR) was performed in order to select molecular descriptors that best describe the retention behavior of the compounds investigated, and to determine the similarities between molecules. MLR equations, that represent the retention measure RMo as a function of the in silico molecular descriptors were established. The statistical quality of the generated mathematical models was determined by standard statistical measures and cross-validation parameters. Obtained results indicate that previously mentioned mathematical models are statistically significant and can successfully predict retention behavior of examined xylofuranose derivatives.