The distant hybridization of mollusk originated from oyster with 130 years' history.Moreover, both the prospects and problems for interspecific hybridization of oyster were summarized on the basis of the numerous attempts and recent research results.Generally, interspecific hybridization can generate transgressive hybrid phenotypes, which have extreme trait values exceeding the combined range of the parental species.Such as increasing growth rate, increasing harvest ability, increasing environmental tolerances, and increasing overall hardiness in culture conditions.Numerous attempts at hybridization in the genus Crassostrea have been reported, most of them suffer from several problems.In this review, the authors summarized up the past of works and pointed out the new aspects as follows:① Confirmation the taxonom of oyster;② Gametic compatibility:including one direction or two directions in fertilization and fertilized strength;③ Evaluating the phenotypic character;④ Genetic identification for hybrids;⑤ Heterosis examination;⑥ Analysis of the patterns of hybrid sterility;⑦ Alloploidy induction;⑧ Interspecific hybridization;⑨ Questions and prospects.Finally, we must indicate that the opinion of unviable hybrid larvae was inaccurate, and a lager number of hybrids were able to obtain in certain environments.Key issues in the interspecific hybridization required to carefully consider and carry out it in the genus Crassostrea.Trustingly, interspecific hybridization will be a good tool to improve phenotypic traits with modifying genes from two parents to the hybrids;and these were made as the excellent research materials for the molecular, cellular and evolutionary biology.