Dunaliella salina(D. salina) has been widely applied in various fields because of its inherent advantages, such as the study of halotolerant mechanism, wastewater treatment, recombinant proteins expression, biofuel production, preparation of natural materials, and others. However, owing to the existence of low yield or in the laboratory exploration stage,D. salinasystem has been greatly restricted for practical production of various components. In past decade, significant progresses have been achieved for research ofD. salinain these fields.Among them,D. salinaas a novel expression system demonstrated a bright prospect, especially for large-scale production of foreign proteins, like the vaccines, antibodies, and other therapeutic proteins. Due to the low efficiency, application of traditional regulation tools is also greatly limited for exploration ofD. salinasystem. The emergence of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system offers a precise editing tool to overcome the obstacles ofD. salinasystem. This review not only comprehensively summarizes the recent progresses ofD. salinain domain of gene engineering but also gives a deep analysis of problems and deficiencies in different fields ofD. salina. Moreover, further prospects of CRISPR/Cas system and its significant challenges have been discussed in various aspects ofD. salina. It provides a great referencing value for speeding up the maturity ofD. salinasystem, and also supplies practical guiding significance to expand the new application fields forD. salina.