Many biological cells appear quasi-spherical, such as red blood cells, white blood cells, egg cells, cancer cells, etc. Cell size is an important basis for medical diagnosis. The traditional method is to use a microscope or flow cytometer to obtain the cell size. Either it depends on professionals and cannot be automated, or it is expensive and bulky, which are not suitable for point-of-care test. Lab-on-a-chip technology using a lensless imaging system gives a better solution for obtaining the cell size. In order to deal with the diffraction in the lensless imaging system, the distance between the light source and the cell, the distance between the cell and the CMOS image sensor and optical wavelength need to be accurately measured or controlled, which will greatly increase the complexity of the system, making it difficult to truly apply to point-of-care test. In this paper, an adaptive parameter model for quasi-spherical cell size measurement based on lensless imaging system is given. First, the diffraction theory used in the model is explained. Then, the adaptive algorithm of the system parameter is given. To illustrate the practicality of the algorithm, a quasi-spherical cell size measurement method and a super-resolution algorithm are given. Finally, the experiment proves that the adaptive parameter model is effective can meet the needs of quasi-spherical cell size measurement.