Silence
Throughout the novel Rodrigues battles with silence in many forms, all of which reflect, to him, God's indifference toward the suffering of himself and the Japanese Christians. The landscape remains silent and unchanged after murders, and God remains silent when called out to for help. Silence represents indifference of the world, and since God is meant to control the world, by extension, God.
Water
Japan, especially the parts Rodrigues travels in, is surrounded by water. Watery imagery is a prominent aspect of Rodrigues's narrative letters because it is a constant in his surroundings and seeps into the way he views the world. Water is often used in similes and metaphors, as well as observations of the landscape. Its placid grayness and stormy blueness often represent the narrator's moods and outlook on his life and God.
Sin
The questions of what is or isn't a sin is prominent in the novel. Rodrigues defines a sin as anything that goes against Christ and God, while other Christians and non-Christians offer differing views of sin, such as standing by and doing nothing while others suffer. One example of this is Rodrigues refusing to apostatize even when his apostasy could save the lives of many Christians in Japan. The struggle to define sin by Biblical rules or human morality forms a central struggle of the novel.
West vs. East
Endo often focuses on the incompatibility of Western Christianity with the East, specifically Japan. Variously referring to Japan as a swamp in which Christianity cannot take root, several characters in the novel believe that Christianity is fundamentally incompatible with Japanese culture. Even when missionaries believed hundreds of thousands of people had converted, their conception of Christianity was not the same as the missionaries intended (and thus not actually Catholicism): they were unable to conceive of a divine Christ, thinking of him instead as an exalted man. This is but one example of many in the novel where Endo focuses on fundamental differences between East and West.
Faces
The face is a theme in Silence, most prominently in Rodrigues's recollections of his love for the face of Christ and inability to trample on the fumie, which bears his image. Rodrigues has always imagined the face of Christ in his mind as the most benevolent, beautiful sight in the world, and returns to his face in times of distress. His inability to apostatize is often driven by his inability to desecrate the face he holds to be most beautiful in the world.
Christinanity
The Christian religion, specifically Catholicism, forms the crux of Silence's plot. Religious zeal drives Garrpe and Rodrigues halfway around the world, and is the only thing to keep their hope alive in otherwise hopeless situations. Christianity is the object of persecution by the feudal Japanese government, which dislikes the meddlesome influence that European missionaries from several countries have had in their spreading of Christianity.
Atheism
When Rodrigues confronts the nearly insurmountable difficulties of his life in Japan and views the suffering all around him, he comes to questions the existence of the God he has always taken as a fact. Doubts begin to creep into his mind and grow ever more forceful over the course of the novel, as he realizes that if there is no God, the sheer futility of his life, the Christians around him, and the many missionaries that came before him is nearly inconceivable.