In the first half of the 15th century, based on the network of trade ports located along the western coast of India, the Bay of Bengal, and Southeast Asia, Portugal began to establish a relationship with Hoi An seaport. For more than a century, the Portuguese made many significant achievements in their maritime commercial and missionary activities in Hoi An. At the same time, Hoi An seaport became one of the places that witnessed the birth of the Latin-based Vietnamese writing system (Quốc ngữ - the Vietnamese national script). In this paper, therefore, the author would like to focus on studying the trade and missionary activities of Portuguese merchants and the Jesuits in Hoi An. On this basis, the author analyses the impact of these activities on the development of Hoi An seaport in the 16th and 17 th centuries. Regarding the above-mentioned goals, mainly historical and logical approaches have been used in combination with comparative analysis of relevant documents.