Flexible actuators are widely used in soft robots, flexible electronics, and biomedicine. However, there still exists a significant challenge in fabricating flexible actuators with multi-response and self-sensing capabilities. In order to address this issue, a novel multi-responsive and self-sensing flexible actuator incorporating an MXene/cellulose nanofibers (MXene/CNF) Janus film was ingeniously developed. MXene/CNF Janus film was prepared using a layered filtration method. The MXene layer of the Janus film exhibits outstanding photothermal conversion properties as well as remarkable electrothermal conversion performance, while its CNF layer showcases excellent moisture absorption properties. As a result of the hydrogen bonding between MXene and CNF, the MXene/CNF Janus film exhibits excellent mechanical properties (Young's modulus of 3620.55 MPa). Using MXene as the printing solution, MXene/polyethylene (MPE) strain sensor with the function of self-sensing the deformation of the flexible actuator was prepared on the PE film by electrohydrodynamic (EHD) printing technology. The MXene/CNF Janus film was assembled with MPE film to fabricate a MXene/CNF-MPE smart flexible actuator with multi-responsive actuation capability and the self-sensing deformation function. Under a near-infrared light intensity of 250 mW/cm, the fabricated actuator can achieve a bending curvature of 1.54 cm within 6.8 s, and it reaches a bending curvature of 4.39 cm within 28 s under a 4 V voltage. Moreover, during the process of environmental humidity changing from 50 % to 80 %, the fabricated actuator demonstrates a bending curvature of 1.81 cm. While responding to these multiple stimuli, the flexible actuator can self-sense the bending deformation through the resistance change of the MPE-based flexible strain sensor. Lastly, the flexible actuator demonstrates the possibilities in gesture recognition of bionic hand and bionic flytrap.