Nanofilm thickness is a critical parameter influencing the performance of micro/nano devices, particularly for films on rough surfaces, where spatially resolved measurements encounter significant challenges such as optical scattering interference and imaging non-uniformity. With the rapid development of micro/nano fabrication technologies, complex nanofilms have become extensively utilized in semiconductor devices, optoelectronics, energy, and sensor applications, increasing the demand for high-precision thickness measurements of large-area, rough-surface films. To address the limitations of conventional methods, including limited scanning areas, long measurement times, susceptibility to scattering interference, and imaging non-uniformity, this paper proposes a novel imaging-based film thickness measurement technique using differential reflection spectroscopy. Firstly, the measurement wavelengths are optimized to enhance measurement efficiency significantly while maintaining accuracy. Secondly, a microscopic optical system with conjugate imaging relationships is designed to ensure precise correspondence between object and image planes, achieving uniform microscopic imaging across centimeter-scale areas. Thirdly, a multi-frame averaging strategy is employed to effectively suppress measurement errors caused by system noise, enhancing the signal-to-noise ratio and stability. Finally, signal compensation using effective medium and phase-change models further enhances the accuracy of nonlinear fitting. Based on the proposed method, an experimental system was established, and thickness measurements were conducted on smooth SiO2/Si, smooth TiO2/Ti, and rough TiO2/Ti samples. The experimental results demonstrate that the proposed system achieves high spatial-resolution and accurate thickness measurement of nanofilms within a rough surface area of approximately 1 cm2, validating its effectiveness and strong practical applicability.