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BACKGROUND: Osteoarthritis is one of the leading causes of global disability and pain. OBJECTIVE: To investigate whether High-Intensity Laser therapy has superior pain-relieving effects in individuals with symptomatic knee osteoarthritis. METHODS: Searches were conducted using CENTRAL, MEDLINE, CINAHL, EMBASE, Web of Science, PEDro, and related reference lists with language limed to English. Clinical trials investigating the effectiveness of High-Intensity Laser therapy compared to other laser therapies, conventional therapies or exercises on knee osteoarthritis pain were included. The screening and selection of studies, data extraction, and methodological quality assessment were performed by two independent researchers. Studies were quantitatively integrated using the Review Manager Software and qualitative analysis using the criteria recommended by the Cochrane Collaboration. RESULTS: Nine studies meeting the eligibility criteria were identified, among which only one study was identified as excellent methodology quality, six was marked as good quality, and the remaining two studies were regarded as fair or poor quality. All studies reported positive effects of High-Intensity Laser therapy on knee osteoarthritis pain. Two studies (136 people) gave indication that there was moderate evidence that High-Intensity Laser therapy could be a promising new possibility in pain relief among patients with knee osteoarthritis compared with sham laser therapy in a short-term treatment (MD, - 2.04, 95% CI, - 2.12 to - 1.96; Z = 51.01, P < 0.01). Four studies (160 people) showed that High-Intensity Laser therapy could be an effective modality on treating pain compared to conventional physiotherapies in decreasing visual analog scale score (MD, - 0.98, 95% CI, - 1.19 to - 0.76; Z = 9.02, P < 0.01). Three studies (123 people) demonstrated that High-Intensity Laser therapy combined with exercises was more effective than placebo laser or lower-intensity laser combined with exercises in alleviating pain in patients with knee osteoarthritis (MD, - 1.54, 95% CI, - 1.84 to - 1.24; Z = 10.06, P < 0.01). CONCLUSION: High-Intensity Laser therapy could be a promising and recommended modality in alleviating knee osteoarthritis pain, especially when it was implemented in combination with exercises. [ABSTRACT FROM AUTHOR]