Tissaphernes (Pers. Cithrafarna), was a Persian soldier and statesman, son of Hydarnes.

In 413 BC he was satrap of Lydia and Caria, and commander in chief of the Persian army in Asia Minor. When Darius II ordered the collection of the outstanding tribute of the Greek cities, he entered into an alliance with Sparta against Athens, which in 412 led to the conquest of the greater part of Ionia. But Tissaphernes was unwilling to take action and tried to achieve his aim by astute and often perfidious negotiations; Alcibiades persuaded him that Persia's best policy was to keep the balance between Athens and Sparta, and rivalry with his neighbour Pharnabazus of Hellespontic Phrygia still further lessened his energy. When, therefore, in 408 the king decided to support Sparta strenuously, Tissaphernes was removed from the generalship and limited to the satrapy of Caria, whereas Lydia and the conduct of the war were entrusted to Cyrus the Younger.

On the downfall of Athens, Cyrus and Tissaphernes both claimed jurisdiction over the Ionian cities, most of which acknowledged Cyrus as their ruler; but Tissaphernes took possession of Miletus, where he was attacked by Cyrus, who gathered an army under this pretence with the purpose of using it against his brother Artaxerxes II. The king was warned by Tissaphernes, who took part in the battle of Cunaxa, and afterwards tried to destroy the Greek mercenaries of Cyrus by treachery.

He was then sent back to Asia Minor to his old position as general in chief and satrap of Lydia and Caria. He now attacked the Greek cities, to punish them for their allegiance to Cyrus. This led to the war with Sparta in 399. Tissaphernes, who once again had recourse to subtle diplomacy, was beaten by Agesilaus II on the Pactolus near Sardis (395); and at last the king yielded to the representations of Pharnabazus, strongly supported by the chiliarch (vizier) Tithraustes and by the queen-mother Parysatis , who hated Tissaphernes as the principal cause of the death of her favourite son Cyrus. Tithraustes was sent to execute Tissaphernes, who was lured to Colossae and slain in 395.