Although single ultra-high-performance indicators have been achieved based on two-dimensional (2D) semiconductors, the comprehensive performances of the photodetectors of them are not so desirable. The response speed and responsivity are two key figures of merit for photodetectors, while these two parameters are always mutually suppressive and can not be synchronously satisfied. Here, we proposed a feasible strategy that can simultaneously improve the responsivity and response speed of In2Se3-based photodetectors by applying the mechanical strain and producing the piezoresistive effect, which can synergistically modulate the band structure and boost the overall photodetecting performances. Through studying the optoelectronic properties of In2Se3 photodetector under strain modulations, we found that the responsivity under 0.65% tensile strain is improved by almost 68.6% on average, while responsivity under 0.65% compressive strain is lowered by about 57.3% in the wavelength range of 200-1000 nm. More importantly, the response speed of the In2Se3-based photodetector under two different mechanical strains rises distinctly (from 244 to 214 and 180 μs, accordingly). The strain-engineering can accommodate the band structure and enhance the electric and optical properties of the semiconducting crystals, ultimately realizing high-performance photodetectors. The strategy proposed in this work for improving the performance of photodetectors provides a promising route to practical applications in next-generation optoelectronic devices.