To improve the germplasm resources of C. semilaevis (Cynoglossus semilaevis), a four-generation consecutive family selection was carried out for fast growth and Vibrio harveyi resistance. Starting from the third generation, we calculated the genomic estimated breeding value (GEBV) of V. harveyi resistance in C. semilaevis through the genomic best linear unbiased prediction and considered the families with high GEBV and infection survival rates as the superior disease-resistant family. In third-generation selection, we obtained 12 superior families. Their average infection survival rate (85.4%) and average GEBV (1.13) were higher than those of the control group (52.2%; 0.27). In fourth-generation selection, 5 families were selected as the superior disease-resistant families, and their average infection survival rate and average GEBV were 71.5% and 0.24, respectively. However, those of the control group were 30.1% and 0.03. After the four-generation consecutive selection, we cultivated the first new variety of C. semilaevis in China using the superior families with disease resistance and fast growth. Compared with the unimproved C. semilaevis population, the new variety “Tayou No.1” had 30.9% increase of survival rate after V. harveyi challenging, the body weight at 18-month-old increased by an average of 17.7%, and the survival rate in rearing improved 15.7% on average. The successful cultivation of C. semilaevis "Tayou No. 1" has added a good variety to the aquaculture breeding industry, promoted the development of the molecular breeding technology of C. semilaevis, and laid a foundation for the application of genomic selection in the aquatic breeding.