Objective: To investigate the effect of Camk4-Egr3 signaling axis on neuronal dendritic development in the hippocampus of congenital hypothyroidism (CH) rats. Methods: The CH model was established in 1-day-old, 7-day-old and 21-day-old SD rats, and divided into CH group and control group. Transcriptome sequencing, Q-PCR and Western Blot were used to detect the expression of Camk4 and Egr3, and immunofluorescence was used to observe the growth of neuronal dendrites. Results: (1) The protein expressions of Camk4 and Egr3 in the hippocampus of the control group increased in a time dependent manner, and the expression of CH group was significantly lower than that of the control group (P< 0.05); (2) After the primary hippocampal neurons were transfected with Camk4 and knocked down, the expression of Egr3 was decreased correspondently, and the mean length of dendrites of hippocampal neurons was decreased compared with the control group. (3) After T3 stimulation of CH primary hippocampal neurons, the protein expression level of Camk4 increased in a time dependent manner. Conclusions: Thyroid hormone deficiency can decrease the expression of Camk4 and Egr3 in the hippocampus of rats, and inhibit the development of neuronal dendrites, suggesting that the Camk4-Egr3 signaling axis plays an important role in the neurodevelopmental abnormalities in the hippocampus of CH rats.