The most direct answer to this question is that the title of the novel encapsulates its theme: the principal choice confronting mankind is that of either to live in a state of freedom, or if this cannot be achieved, to die. That said, the way in which Kazantzakis elaborates the theme, and the story he uses as a vehicle to express it, need to be discussed in order to understand the larger points he is making about men and women, and life and death.
Freedom or Death is set in Crete in the years 1889-91. The basic subject is the ongoing struggle by the Greek population of the island to free itself from the Ottoman Empire. Though mainland Greece had achieved independence in 1829, Crete, as well as the Greeks of Anatolia (Asia Minor) and other non-Muslim ethnic groups, such as the Armenians and Assyrians, still lived under Ottoman rule at this time. In Crete, there had been periodic uprisings by the Greeks throughout the nineteenth-century which had been unsuccessful. The Cretans felt themselves insufficiently supported by mainland Greece, a country at that time which had little power. The only countries in a real position to help them were those of Western Europe, who at the time Freedom or Death takes place still wanted to keep the Ottoman Empire intact and offered nothing but talk and empty promises to the Cretans and the other ethnic groups wishing to achieve independence.
In the novel, the ongoing tension between Greeks and Turks breaks into full-scale ethnic warfare in the aftermath of a dispute between Nuri Bey, a wealthy Turk, and Captain Michales, the de facto leader of the Greek population. Though they had earlier sworn blood brotherhood, Nuri is envious of Michales, and later, a fight breaks out between Nuri and a man named Manusakas, whom the Turks have accused of insulting Islam. Nuri stabs the Greek man to death, but is himself maimed in the fight, and later commits suicide. The situation is complicated by the fact that Nuri's wife Emine, a Circassian (another Muslim people), is having an affair with a Greek man and intends to convert to Christianity.
Violence, ethnic conflict, and the manner in which traditional male ideas of honor and dominance are expressed, form the core of the novel's subject matter. In the nineteenth-century eastern Mediterranean world, loyalty to one's nation and religion are the primary virtues. The single flawed action of Captain Michales occurs when he leads his men on a raid to recover Emine after she has been kidnapped, and thereby deserts his position where he is guarding a church. The Ottomans then burn the church, and Michales does not forgive himself for having allowed his concern for a woman to make him commit such an error. At the end of the story, even after a fragile peace has been established between Greeks and Turks, Michales vows to continue the struggle, remaining in the mountains with a handful of others. At the end, he and his small group are besieged and wiped out by the Turkish forces.
Kazantzakis, as a native of Crete himself and a Greek nationalist, views the heroic struggle against the Ottomans as an existential one in which the motto, repeated again and again throughout the book—Freedom or Death—is the only concept that makes any sense in a brutal, irrational world. Yet the primacy of ethnic and religious conflict is not something taken for granted. As Michales's aged father is dying, he summons his friends and family to his bedside and asks them repeatedly what the meaning of all of this is, the eternal questions of who we are and where we come from. The perpetual struggle between Greeks and Turks is emblematic of the entire history of mankind. When peace is restored, enemies are friends again and the Turkish pasha and the Greek Metropolitan celebrate together with a raki, coffee, and cigarettes. So in the end, Kazantzakis leaves, at the heart of his story, the unanswered question, the unsolved riddle of life and of the universe.