In this study, the therapeutic effect of methylphenidate hydrochloride combined with ω-3 polyunsaturated fatty acids (ω-3 PUFA) for attention deficit hyperactivity disorder (ADHD) in children was investigated. Sixty-eight children with ADHD were randomly divided into control and observation groups, with 34 cases in each group. Both groups were given integrated training of hearing, vision and feeling. On this basis, the control group was treated with methylphenidate hydrochloride, and the observation group was treated with hydrochloride combined with ω-3 PUFA. The treatment in each group was continued for three months. After treatment, compared with control group, in observation group the Swanson, Nolan and Pelham Rating Scale-IV scores were significantly decreased, resp. (p < 0.05), the Wechsler Intelligence Scale for Children-Revised scores were significantly increased, resp. (p < 0.05), and the serum prolactin and 25-hydroxyvitamin D levels were significantly increased, resp. (p < 0.05). The incidence of adverse reactions had no significant difference between two groups (p > 0.05). In conclusion, methylphenidate hydrochloride combined with ω-3 PUFA can effectively improve the symptoms of ADHD in children, and regulate the blood prolactin and 25-hydroxyvitamin D levels.