Abstract: The structural modification of natural product represents a powerful tool for anti-cancer drug discovery. Noscapine, as a phthalideisoquinoline alkaloid from opium, has been used as an over-the-counter antitussive drug with excellent oral bioavailability and low toxicity. Recently, the potential of this compound as a particularly attractive lead for anti-cancer drug discovery has been demonstrated. Multiple mechanisms, especially the interference of tubulin polymerization, might be involved. Thereafter, various structural modifications based on semisynthetic routes, which aims to improve the anti-cancer activity and pharmacokinetic properties, as well as to probe the mechanism, has been performed. Several analogues are emerging as possible candidates as novel anticancer therapies. This perspective mainly discusses the advancing noscapine and related analogues in the fight against malignant disease in recent years. Furthermore, the future directions of this evolving field were also preliminary prospected.