As a core institutional guarantee for developing a unified national market, the negative list system for market access is a key driver to deepen domestic intra-product division of labor and build independent and controllable industrial and supply chains. Against the backdrop of building a unified national market, this paper explores the impact of market access reform on domestic intra-product division of labor and its underlying mechanisms. The results show that the negative list system for market access significantly deepens domestic intra-product division of labor. Mechanism analysis reveals that this system facilitates the two-way flow of factors on the supply side and expands market scale on the demand side, thereby advancing the refinement of domestic intra-product division of labor. Heterogeneity analysis indicates that the negative list system strengthens the release of comparative advantages, promotes regional balanced development, and facilitates the organic integration of an effective market and a proactive government, namely, it exerts a more significant deepening effect on domestic intra-product specialization in regions characterized by lower capital-labor ratios, higher levels of government intervention, lower market vitality, as well as in central and western China. This study clarifies the institutional effects of market access reform on intra-product division of labor. Amid the profound restructuring of global value chains, it also offers policy implications for empowering the development of a unified national market and fostering a modern industrial and supply chain system through institutional reform and innovation in the market.