This research clarifies the crucial role of NSD3 in lung adenocarcinoma that is correlated with NSD3/PPP1CB/p‐STAT3 dimer formation, revealing the correlation between non‐epigenetic functions of NSD3 and tumor cell metabolism, suggesting the potential of NSD3 in targeted therapy in lung adenocarcinoma. Here, PPP1CB is linked to lung adenocarcinoma.