Lung cancer is a major cause of cancer-related deaths worldwide, and it poses a significant threat to global health due to its high incidence and mortality rates. There is an urgent need for better prevention, early detection, and effective treatments for this disease. The treatment options for lung cancer depend on various factors such as the stage of the disease, the type of cancer, and the patient's overall health. Currently, the primary treatment strategies include surgery, chemotherapy, radiation therapy, targeted therapy, immunotherapy, and combination therapies. Berberine, a natural alkaloid found in medicinal plants, has demonstrated potential as an effective anti-cancer agent against lung cancer. The present study aims to summarize the evidence supporting Berberine's ability to inhibit the growth of lung cancer cells, induce apoptosis, and slow down tumor growth in both laboratory and animal studies. The study also shed light on the complex molecular mechanisms involved in its anti-tumor effects, including its impact on signaling pathways, DNA repair systems, and interaction with non-coding RNAs, all of which contribute to tumor suppression. Additionally, the synergistic effects of Berberine with other natural compounds and chemotherapy drugs are discussed. Overall, its multifaceted approach and proven effectiveness justify further research to develop Berberine into a viable treatment option for lung cancer patients. Abbreviations: BBR, Berberine; EMT, epithelial-mesenchymal transition; NSCLC, non-small cell lung cancer; ROS, reactive oxygen species; ASK1, Apoptosis Signal-regulating Kinase 1; JNK, c-Jun N-terminal kinase; BHC, Berberine Hydrochloride; DSB, double-strand breaks; CSN, COP9 signalosome; NIR, near-infrared; LLC, Lewis lung carcinoma; RTK, receptor tyrosine kinase; B-Phyt-LCNs, Berberine-Phytantriol liquid crystalline nanoparticles; ER, endoplasmic reticulum; Ber-LCNs, Berberine-loaded liquid crystalline nanoparticles; BNS, Berberine nanostructure; BER-CS-NPs, Berberine-loaded chitosan nanoparticles; B-Phyt-LCNs, Berberine-Phytantriol liquid crystalline nanoparticles; B-Phyt-LCNs, Berberine-loaded liquid crystalline nanoparticles; Ber-LCNs, Berberine-loaded liquid crystalline nanoparticles; B-ZnO NPs, Berberine-loaded zinc oxide nanoparticles; B-C60, Berberine-C60 complex; LTP, Low-Temperature Plasma.