Cross-border E-commerce has become the main way for Chinese small and medium-sized enterprises (SMEs) to enter the international market. As a pioneer in the development of cross-border E-commerce in China, Guangdong has issued many policies to encourage SMEs to carry out cross-border E-commerce. Taking SMEs in Guangdong as the research object, the structural equation model is used to explore the influence of external factors on enterprises’ willingness to launch cross-border E-commerce. It is found that cross-border E-commerce marketing, customs clearance, logistics, policies and talents have a significant and positive impact on the willingness of Guangdong SMEs to carry out cross-border E-commerce, while cross-border E-commerce electronic payment has no significant impact. Finally, corresponding suggestions for policy and industry are put forward.