Objective To investigate the effects of Levetiracetam add-on therapy on cognitive function and serum nerve factor levels of young patients with refractory epilepsy and its safety. Methods A total of 110 young patients with refractory epilepsy admitted to The Third Affiliated Hospital of Sun Yat-Sen University Yuedong Hospital from January 2019 to December 2020 were divided into the control group (55 cases, treated with phenobarbital and carbamazepine) and the observation group (55 cases, combined with levetiracetam add-on therapy on the basis of the control group) according to the random number table method, both groups were treated for 6 months. The clinical efficacy, Montreal Cognitive Assessment Scale (MOCA) score, Quality of Life Scale (QOLIE-31) score, serum levels of brain-derived neurotrophic factor (BDNF), neuron-specific enolase (NSE) and myelin basic protein (MBP) of patients 3 and 6 months after treatment and the incidence of adverse reactions during treatment of patients in the two groups were compared. Results Compared with the control group, the total clinical effective rate was higher than that in the observation group 3 and 6 months after treatment, and the MOCA score, QOLIE-31 score, serum BDNF levels of patients in the two groups 3 and 6 months after treatment increased compared with before treatment, and the observation group was higher than the control group; the serum NSE and MBP levels of patients in the two groups 3 and 6 months after treatment decreased compared with before treatment, and the observation group was lower than the control group; compared with the control group, the total incidence of adverse reactions in the control group was 30.91%, and the observation group (10.91%) decreased significantly compared with that in the control group (all P <0.05). Conclusion Levetiracetam add-on therapy in the treatment of young patients with refractory epilepsy can effectively relieve clinical symptoms, inhibit epileptic seizures, improve cognitive function, increase the content of neuroprotective factors in brain tissue, alleviate nerve tissue damage, and improve the quality of life and treatment safety.