The protein extracted from red algae has various biological activities, including anti‑inflammatory, anticancer, antioxidant, and antiobesity properties. However, the effects of (PYCP) on tumor necrosis factor‑α (TNF‑α)‑induced muscle atrophy are unknown. Therefore, the present study investigated the protective effects and related mechanisms of PYCP against TNF‑α‑induced myotube atrophy in C2C12 myotubes. Treatment with TNF‑α (20 ng/ml) for 48 h significantly reduced myotube viability and diameter and increased intracellular reactive oxygen species levels; these effects were significantly reversed in a dose‑dependent manner following treatment with 25‑100 g/ml PYCP. PYCP inhibited the expression of TNF receptor‑1 in TNF‑α‑induced myotubes. In addition, PYCP markedly downregulated the nuclear translocation of nuclear factor‑κB (NF‑κB) by inhibiting the phosphorylation of inhibitor of κB. Furthermore, PYCP treatment suppressed 20S proteasome activity, IL‑6 production, and the expression of the E3 ubiquitin ligases, atrogin‑1/muscle atrophy F‑box and muscle RING‑finger protein‑1. Finally, PYCP treatment increased the protein expression levels of myoblast determination protein 1 and myogenin in TNF‑α‑induced myotubes. The present findings indicate that PYCP may protect against TNF‑α‑induced myotube atrophy by inhibiting the proinflammatory NF‑κB pathway.