In 1539, Ignatius was asked by the Pope to send two men to the Portuguese colonies in the East. When Bobadilla fell ill, Ignatius asked Francis to substitute him. He left Lisbon on 7 April 1541 and reached Goa on 6 May 1542. The Primary mission of Francis, as ordered by King John III, was to restore Christianity among the Portuguese settlers. Francis Xavier devoted much of his life to missions in Asia, mainly in the four centers of Malacca, Amboina and Ternate, Japan, and off-shore China. It then dawned upon him that he would have to go to the places that were centers of influence for the whole region. He felt that all these areas were interconnected; they could not be evangelized separately. He cared for the ill in the Royal hospital, and preached in the streets for the conversion and salvation of Hindu, Jewish, and Muslim souls.
Upon arrival in Goa, he gave much of his time to the teaching of children. He spent the first five months in preaching and ministering to the sick in the hospitals. After that, he walked through the streets ringing a bell to summon the children and servants to catechism. He was invited to head Saint Paul's College, a pioneer seminary for the education of secular priests, which became the first Jesuit headquarters in Asia.
Francis Xavier also sailed to Cochin, the Malabar coast, Tamil Nadu, and as far as Malacca and Japan. During the journeys, many miracles were attributed to him. A few among these include turning casks of sea water into fresh water for sailors, and bringing a boy back to life after he had fallen overboard.
Francis Xavier soon got to know that along the Pearl Fishery Coast, which extends from Cape Comorin on the southern tip of India to the island of Mannar, off Ceylon (Sri Lanka), there were people called Paravas. Many of them were baptized ten years before, inorder to please the Portuguese who had helped them against the Moors, but remained uninstructed in the faith. Accompanied by several native clerics from the seminary at Goa, he set sail for Cape Comorin in October 1542. He taught those who had already been baptized, and preached to those who weren't. His efforts with the high-caste Brahmins remained unavailing. He devoted almost three years to the work of preaching to the people of southern India and Ceylon, converting many. He built nearly 40 churches along the coast, including St. Stephen's Church, Kombuthurai, mentioned in his letters dated 1544.