Muscle tenderness is an important complex trait for meat quality and thus for genetic improvement through animal breeding. However, the physiological or genetic control of tenderness development in muscle is still poorly understood. In this work, using transcriptome analysis, we found a relationship between gene expression variability and tenderness. Muscle (longissimus dorsi) samples from 30 F2 pigs were characterized by Warner–Bratzler Shear Force (WBSF) on cooked meat as a measurement of muscle tenderness. Gene expression levels were measured using microarrays for 17 muscle samples selected to represent a range of WBSF values. Using a linear regression model, we determined that samples with WBSF values above 30 N could be effectively analysed for genes exhibiting a significant association of their expression level on shear force (false discovery rate <0.05). These genes were shown to be involved in three functional networks: cell cycle, energy metabolism and muscle development. Twenty-two genes were mapped on the pig genome and 12 were found to be located in regions previously reported to contain quantitative trait loci (QTL) affecting pig meat tenderness (chromosomes 2, 6 and 13). Some genes appear therefore as positional candidate genes for QTL.