With worldwide industrialization, red tide events have been reported more frequently and their harm to humans has become increasingly severe. Although great efforts have been made to elucidate the ecology and biology of red tide events, studies of their molecular mechanisms are still limited, including those of the mechanisms involved in the decline phase of red tide. Alexandrium catenella is an important causative dinoflagellate associated with harmful algal blooms and paralytic shellfish poisoning. In this study, a growth decline specific cDNA library of A. catenella was constructed using suppression subtractive hybridization (SSH) technology to identify genes expressed in response to decreased growth of red tide algal cells as a primary step in elucidating the red tide process. Samples collected during the decline phase of growth were analyzed and compared with those collected during other phases of growth, which were considered to be controls. A total of 800 clones were obtained from the SSH library, and 556 positive clones were identified by nested PCR. Dot blot hybridization was conducted to screen differentially expressed genes from the positive clones, and a total of 160 differentially expressed clones were identified. After sequencing and classification, 21 sequences were obtained, six of which were found to be homologous with functional genes in the NCBI database. Specifically, these genes were homologous with CHK1 checkpoint-like protein, exosomal 3'-5' exoribonuclease complex, glutaredoxin, Na⁺/ K⁺ ATPase, chloroplast gene and pG1 protein. The remaining sequences did not match any present functional genes in the database and were therefore assumed to be novel. Checkpoint is a biochemical process that detects DNA damage or problems during DNA replication and restricts problematic cells by maintaining them in certain cell phases or inducing apoptosis. Chk1 is a serine/threonine kinase that functions as an important signal transducer in the DNA damage process. Glutaredoxin can regulate intracellular redox balance and resist oxidative damage response. Na⁺/ K⁺ ATPase is widely distributed in the cell membrane, where it regulates the Na⁺, K⁺ concentration gradient to maintain the electrical charge over the cell membrane. There is increasing evidence indicating that ion dynamic balance involves the cell apoptosis process. Because Na⁺/ K⁺ ATPase is the primary system used to acquire K⁺, the functional loss of this enzyme and disorder of ion dynamic balance are clarified as critical symbols for the induction of apoptosis and disease produced by apoptosis. Degradation of mRNA is an important step in regulation of gene expression in eukaryotes. The degradation of mRNA can be divided into degradation of normal and abnormal transcripts. The degradation of abnormal transcripts is a method of maintaining normal physiological function. At present, a large number of studies have indicated that exosomal 3'-5' exoribonuclease plays an important role in the mRNA degradation process. The function of the pG1 protein is not currently available. However, considering its high frequency within sequencing reports, the gene is highly transcribed. Based on the analysis conducted in this study, we speculate that the growth decline of A. catenella involves processes of DNA damage, mRNA degradation, redox status changes, ion dynamic equilibrium and changes in the chloroplast physiological status. This study will help us to better understand the decline mechanism of red tide algae, and provide a foundation for studying the molecular biological mechanism of red tide dynamics and developing possible methods to monitor and control red tide.