Persian satrap (governor) who played a leading part in Persia's struggle to reconquer the Ionian Greek cities of Asia Minor that had been held by Athens since 449.

In 413 Tissaphernes, who was then satrap of Lydia and Caria, formed an alliance with Sparta, and by the next year he had regained most of Ionia. Fearing that a complete victory of Sparta over Athens in the Peloponnesian War would endanger Persian interests, he supplied only limited assistance to his ally. As a result, when the Persian king Darius in 407 decided to support Sparta fully, Tissaphernes was replaced as commander in chief in Asia Minor and as satrap of Lydia by Darius' son, Cyrus The Younger, and his influence was limited to the satrapy of Caria. Cyrus revolted, however, shortly after his brother Artaxerxes (Artaxerxes II) took the throne.

Tissaphernes, supporting Artaxerxes, distinguished himself in the Battle of Cunaxa (401), where Cyrus was killed, and afterward treacherously seized the leaders of Cyrus' Greek mercenaries. Reinstated as satrap of Caria and Lydia, he attacked the Ionian cities, control of which had been lost during Cyrus' revolt. This attack led to war with Sparta, and, after Tissaphernes' severe defeat at Sardis in 395, his enemy Parysatis, mother of Cyrus, succeeded in persuading Artaxerxes to have him executed.