With the rapid developing of economic globalization and digital economy, cross-border e-commerce has become an important business model. Cross-border e-commerce, a new and productive business model, which has various legal loopholes because it is still in the process of development. MNEs are increasingly avoiding taxes through cross-border e-commerce, excessive tax avoidance leads to tax evasion, affecting the tax interests of various countries, and is not conducive to world economic stability. This research mainly uses the case analysis method, comparative analysis method and literature analysis method, focusing on the tax avoidance methods of cross-border e-commerce and the anti-tax avoidance legal regulation, and finds the shortcomings of cross-border e-commerce in the existing legal norms. At present, many countries do not have legislative documents for cross-border e-commerce, tax legislation on cross-border e-commerce is close to the blank, the types of taxes, taxation methods and tax supervision of various countries are not clear, and there is a lack of a complete and scientific tax mechanism. Cross-border e-commerce of MNEs takes advantage of legal loopholes, mainly adopting tax avoidance methods such as registering companies in international tax havens, transfer pricing and using electronic information technology. WTO, OECD, EU and the US proposed anti-tax avoidance regulations for cross-border e-commerce earlier, which can provide legislative reference for other countries and international organizations. In order to promote the sound development of economic globalization and digital economy, countries should strengthen cooperation, establish a complete tax information exchange mechanism, improve legal norms related to cross-border e-commerce, and adopt a more scientific and effective tax collection and supervision mechanism for tax authorities.