Alexander Liholiho 'Iolani was born on Feburary 9, 1834. His mother,the daughter of Kamehameha I, was the High Chiefess Kina'u. His father on the other hand, was High Chief Kekuamao'a, the governor of O'ahu. His grandfather was King Kamehameha I. He was the fourth born. His older brothers were David Kamehameha, Moses Kekuaiwa, and Lot Kapuaiwa. His younger sister was Victoria Kamamalu.

Alexander later became the son of Kamehameha III and his wife Kalama. He joined the Chiefs' Children's School when he was the age of six. As a result of his skills in academics, he was translating land deed from Hawaiian to English when he was only thirteen. He was also translating news articles for the local newspaper when he was the age of fourteen. He was also very talented at math and science. He left the school when he was fourteen.

Kamehameha III died when he was twenty years old, leaving him with the rule of the Hawaiian Kingdom. Alexander Liholiho married to his childhood sweetheart Emma Na'ea Rooke on June 19, 1856. Emma's parents were Fanny Kekelaokalani Young and George Na'ea. They gave birth a son on May 20, 1858. They named him Albert Edward after the husband of Queen Victoria of England, and Alexander's father Kauikeaouli. He died on August 27, 1862 at only four years old.

The Queen's Hospital was founded by Alexander Liholiho due to the fact that many of the Hawaiian people were dying from diseases. He and his wife raised a total of thirteen thousand dollars after asking pledges from Hawaiians and foreigners.