Optimal skeletal muscle mass is vital to health as defects in muscle protein metabolism underlie or exacerbate human diseases. The mTORC1 is a critical regulator of mRNA translation and protein synthesis. These functions are mediated in part by the ribosomal protein S6 kinase 1 (S6K1) through mechanisms that are poorly understood. The tumor suppressor programmed cell death 4 (PDCD4) has been identified as a novel substrate of S6K1. Here, we examined the expression of PDCD4 in skeletal muscle and its regulation by nutrition. Male rats (~100g, n = 6) were subjected to feed deprivation (FD) for 48 h; some rats were re‐fed for 2 h. FD suppressed muscle protein synthesis and serine 67 phosphorylation of PDCD4 (−50%) but increased PDCD4 abundance (P<0.05); re‐feeding reversed these changes (P<0.05). Consistent with these effects being regulated by S6K1, activation of this kinase was suppressed by FD (−91%, P<0.05) but was increased by re‐feeding. Gavaging rats subjected to FD with a mixture of amino acids (AA) restored muscle protein synthesis and reduced PDCD4 abundance relative to FD (P<0.05). Finally, when myoblasts were grown in AA‐ and serum‐free medium, rates of proteins synthesis in cells depleted of PDCD4 more than doubled the values in cells with a normal level of this protein (P<0.0001). Thus, AA stimulate protein synthesis in skeletal muscle in parallel with the reduction of the abundance of PDCD4.