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Peripheral nerve injury is encountered quite commonly in the clinic, and treatment results are often not satisfactory. Therefore, promoting nerve regeneration and functional recovery is a primary goal of neuroscience research. Recovery of corresponding target muscle can differ following peripheral nerve injury, but the reasons are unknown. Herein, we investigated differential gene and protein expression in gastrocnemius and tibialis anterior muscle following tibial and common peroneal nerve injury using RNA sequencing and proteomics approaches, and analysed the results by bioinformatics. In total, 1794, 1765, 1656 and 2006 differential genes and 398, 400, 959 and 472 differential proteins were identified in gastrocnemius and tibialis anterior muscles at 1, 7, 14 and 21 days after surgery, related to activation of 51 signalling pathways. Differential expression of these genes and proteins may contribute to the degree of recovery of target organs following peripheral nerve injury. The findings provide a foundation for investigating regeneration mechanisms following peripheral nerve injury. • It is first to explore the expression of genes and proteins in the corresponding target muscles after nerves injury. • It is first to explore the differential expression of genes and proteins in tibial and common peroneal nerves after injury. • It explores the expression of differential genes and proteins by RNA sequencing and proteomics techniques. • It suggests that different nerves have different gene and protein expressions in respective muscle tissues after injury. [ABSTRACT FROM AUTHOR]