Related research findings indicated that the hardness of the tail meat from red swamp crayfish (Procambarus clarkii) increased when responding to cold stress during the transportation. However, the effect of low temperature on crayfish muscle was still at the phenotype level, there were few studies on the molecular mechanism of crayfish muscle response to cold stress. The effect of cold stress on the tail meat of crayfish during simulated transportation (control and low temperature stress for 12 h (LT_12), 24 h (LT_24) and 36 h (LT_36) at 4 ℃) were investigated by integrated transcriptome and proteomics. The results showed that the hardness of crayfish meat increased after cold stress. Gene ontology (GO) analysis showed that differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) of crayfish coping with cold stress were mainly involved in metabolism and glycolysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic analysis found that the metabolic response to cold stress included changes in amino acids such as valine and isoleucine. Low temperature activated glycolysis and amino acid metabolism pathway as well as peroxisome pathway to maintain body balance. The significant increase in the expression of cytoskeletal protein-actin related genes such as β-actin and ACT1 might cause the increase of muscle hardness under stress.