The world population has been continuously increasing and has led to the growing demand for rice. It is therefore important to pay as much attention to the enhancement of grain yield as well as grain quality. Grain size is one of the major factors determining grain yield and quality. A large number of genes are known to be involved in regulation of grain size. However, the influence of their haplotype combination is still largely unknown. Of the previously characterized genes, we especially focused on the six genes (GS3, GS5, GS6, GW2, qSW5/GW5, and GW8/OsSPL16) to expand our understanding of regulation of grain size and to develop a regression equation model that can be used for molecular rice breeding. A total of 215 rice germplasms, which originated or developed from 28 rice-consuming countries, were used in this study. The genotyping analysis revealed that different alleles of the six genes were widely distributed in our germplasm collection and also showed significant associations with the differences in grain size. Interestingly, we found that the relatively small number of haplotype combinations preserved in diverse rice germplasms and showed significant associations with the differences in grain size. In addition, we also found that a single gene-specific allelic variation plays an important role in regulation of grain size in the presence of a certain type of haplotype combination. Based on these results, we developed a regression equation model for prediction of rice grain size. We expect that our model can be used for rice molecular breeding to develop new rice varieties having a grain size in a particular range.