It is well-known that DC-DC boost converters are cascaded with DC-AC inverters for grid connection of the photovoltaic (PV) systems. In the traditional control approaches, the mentioned DC-DC and DC-AC converters are controlled separately to facilitate the controller design problem. However, from the controller design viewpoint, the overall structure of the grid connected PV generator is a multi-input multi-output (MIMO) system. The duty-cycle of the DC-DC converter and Inverter modulation index are the control inputs and on the other hand, generated photovoltaic DC power, and exported power to the grid are control outputs. Moreover, the inverter DC link voltage should be stabilized by the closed-loop controller as well as an internal control output. If controllers are designed separately, it means that the interaction between DC-DC and DC-AC controllers isn’t considered accurately and since the isolated models of DC-DC converter and DC-AC inverter are extracted based on some approximated assumptions, separate controller design cannot guarantee stability and robustness of the whole system in a wide range of operation. To cope with these problems, in this paper, a novel MIMO sliding mode controller (SMC) is developed for comprehensive closed-loop control of the DC-DC boost converter cascaded with a single-phase DC-AC grid connected photovoltaic inverter. In the proposed approach, the dynamic model of whole system is developed comprehensively at first and then a unique MIMO controller is designed to control both DC-to-AC and DC-to-DC converters together. To cope with the nonlinear characteristic of the system and uncertainty of model parameters in a wide range, a fixed-frequency SMC is developed using the comprehensive state space model of the closed loop system. In the proposed MIMO-SMC controller, the AC power (which is exported to the grid) and operating point of the PV source are controlled via inverter modulation index and duty cycle of the DC-DC boost converter respectively. Another major advantage of the proposed system is mitigating the non-minimum phase characteristic of the boost converter through the indirect control of inverter DC link capacitor. To evaluate the performance of the designed control system, simulation results are compared with a standard linear PI controller. It is shown that the developed system has zero steady-state error and enjoys faster dynamic response during the start-up and step changes of AC and DC current references. Moreover, it can maintain the stability of closed-loop systems in a wide range of operations.