Berberine exerted anti-cancer effect in various cancer cell lines, and was also implied in the treatment of metabolic related diseases. Given the metabolic modulation, we hypothesized that berberine possessed anti-cancer effect under the assistance of metabolic interference. Working as a modulator, metabolic enzyme inhibitor or complex network regulator in energy metabolism, berberine was highlighted in current cancer research. A reasonable cross talk between Chinese medicine and energy homeostasis provided a solid foundation for berberine interference on cancer cells reprogramming metabolism. Our result showed that berberine regulated the reprogramming metabolism through three aspects simultaneously, including mitochondrial oxidative phosphorylation, glycolysis and macromolecular synthesis. This interference with reprogramming metabolism was a continuous, simultaneous and sustainable approach in a moderate mode. And it could be regarded as a gentle and virtuous cycle from a multi-level perspective, indicating an integrated approach in cancer therapy. Meanwhile, we thought that Chinese medicine could link cancer and metabolic related diseases from a dynamic perspective through integrated network pharmacology. This cross talk would be a realistic and significant strategy for anti-cancer drug discovery and needs further investigation in future. © 2015 Bentham Science Publishers