There is a growing interest among clinicians and researchers in identifying potential biomarkers associated with autism. Neurofilament light chain (NfL) and Tau protein, which are proteins associated with neurodegeneration and neuroaxonal degeneration, are particularly promising potential biomarker candidates in this field. In this study, we compared serum NfL (sNfL) and serum Tau (sTau) levels in ASD patients, their healthy siblings (HS), and healthy controls (HC), aimed to investigate their relationship with ASD severity. Our study included 43 ASD-diagnosed participants, 43 HS participants and 42 HC participants. Clinical characteristics of the participants were assesed by Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS), Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and Strengths and Difficulties Questionnaire (SDQ). Serum samples were subjected to analysis via enzyme-linked immunosorbent assay (ELISA) to quantitatively measure the levels of NfL and Tau protein. sNfL levels in the ASD group were significantly higher than both of the control groups. Regarding sTau levels, no significant difference was found between study and control groups. In addition, NfL and Tau levels were not significantly correlated with ASD symptom severity. Our findings may indicate that the sNfl levels associated with neuroaxonal damage may constitue a potential clinical biomarker rather than being an endophenotype phenomena.