This study aimed to determine the therapeutic effect of radiofrequency combined with low-dose collagenase injected into the disc interior via an anterior cervical approach for cervical intervertebral disc herniation.Forty-three patients (26-62-year old; male/female ratio: 31/12) with cervical intervertebral disc herniation received radiofrequency combined with 60 to 100 U of collagenase, injected via an anterior cervical approach. The degree of nerve function was assessed using the current Japanese Orthopaedic Association (JOA) scoring system at 3 and 12 months postoperation. A visual analogue scale (VAS) was used to evaluate the degree of pain preoperation and 7 days postoperation. The preoperative and 3 month postoperative protrusion areas were measured and compared via magnetic resonance imaging (MRI) and picture archiving and communication systems (PACS).Compared with the preoperative pain scores, the 7-day postoperative pain was significantly reduced (P <0.01). The excellent and good rates of nerve function amelioration were 93.0% and 90.7% at 3 and 12 months postoperation, respectively, which was not significantly different. Twenty-seven cases exhibited a significantly reduced protrusion area (P <0.01) at 3 months postoperation. No serious side effects were noted.To our knowledge, this is the first study to demonstrate that the use of radiofrequency combined with low-dose collagenase injection into the disc interior via an anterior cervical approach is effective and safe for the treatment of cervical intervertebral disc herniation.