To reduce the effect of noise on inversion result of grain diameter in nano-particle diameter measurement using photon correlation spectroscopy, a nano-particle diameter computing method is proposed based on photon correlation spectroscopy with nonnegative least squares. Photon correlation spectroscopy itself is as the weight to derive discrete model of inversion algorithm and avoid the influence of data fluctuation close to zero. The 90 nm, 190 nm and mixed latex particles are measured by the photon correlation spectroscopy equipment and compared with the traditional nonnegative least squares. The 30 experimental data in 60 seconds indicate that in the inversion of unimodal paticle group, the results of present method is close to traditional nonnegative least squares but variance of multiple repeated measurement is smaller which proves good repeatability of present method; in the inversion of multimodal particles, the results of present method are much closer to true values of diameters, however, the results of nonnegative least squares deviate more from true values. Experimental data of different measurement time show that in a short period of time, variance of present method is smaller and it can obtain more accurate results in a shorter period of time.