The invention discloses a high-precision hybrid integrated circuit test frame isolation protection structure, which relates to the technical field of circuit test auxiliary structures. The high-precision hybrid integrated circuit test frame isolation protection structure integrates a single-chip microcomputer, a test chip, a relay, an isolation optocoupler and a Handle interface on a circuit substrate, realizes short circuit detection between a test frame power supply and the ground and isolation between the test frame power supply and a to-be-tested chip power supply by utilizing the optocoupler, can prevent the chip from being damaged by hot plugging, facilitates the installation and improves the use efficiency, isolates all analog power supplies and digital power supplies as well as analog grounds and digital grounds by means of the optocoupler, suppresses common-mode interference, avoids common-mode interference generated during integrated design, ensures system signal stability and normal overall operation, reduces the system size, decreases the cost, improves the efficiency, can measure whether the power supply of the chip and the ground are short-circuited or not, and isolates the power supply and an instruction signal by adopting the optocoupler, so that crosstalk is prevented.