In a hydraulic drive system for a construction machine, first flow control mechanism includes first and second flow control valves (11a, 11b) and first interlock mechanism (54, 55) for interlocking the first and second flow control valves with first directional control mechanism (7), and second flow control mechanism includes third and fourth flow control valves (12a, 12b) and second interlock mechanism (56, 57) for interlocking the third and fourth flow control valves with second directional control mechanism (9). First pressure control mechanism includes at least first pressure control valve (13a) operated in response to a pressure signal in a valve-closing direction, and second pressure control mechanism includes only second pressure control valve (15b) operated in response to the pressure signal in a valve-closing direction. A first hydraulic pump (25a) is connected to a first actuator (19) via the first flow control valve (11a), the first pressure control valve (13a) and the first directional control mechanisms (7), and a second hydraulic pump ( 25b) is connected to the first actuator (19) via the second flow control valve (11b) and the first directional control mechanism (7). The first hydraulic pump (25a) is also connected to a second actuator (21) via the third flow control valve (12a) and the second directional control mechanism (9) in parallel to the first actuator (19) without passing any pressure control valve, and the second hydraulic pump (25b) is also connected to the second actuator (21) via the fourth flow control valve (12b), the second pressure control valve (15b) and the second directional control mechanism (9) in parallel to the first actuator (19).