This is a multi-center, randomized, open-label, parallel-arm phase IV clinical study, for which a total of 300 patients with mild to moderate knee osteoarthritis will be enrolled. In the first 4 weeks (run-in period), the subjects will receive on-demand treatment with Diclofenac Sodium Sustained Release Tablets (DICL-SR) 75mg, quaque die（QD）. After the run-in period, the subjects, if their knee pain has not worsened to a level requiring surgical treatment, will be randomized to two groups in 1:1 ratio: one group receiving Artz® via intra-articular injection (once weekly, for 5 consecutive weeks) in combination with DICL-SR 75mg,quaque die（QD）, for 12 consecutive weeks on demand. The other group receiving DICL-SR 75mg alone,quaque die（QD）, for 12 consecutive weeks on demand. DICL-SR 75mg quaque die（QD） may be administered to the subjects of both groups on demand as long as they have a knee pain. If the knee pain has disappeared, this drug may be withdrawn. However, if the pain occurs again and requires treatment, oral administration of DICL-SR may be resumed. A subject is allowed to withdraw from this study prematurely if unable to tolerate the adverse effects.

A total of 8 visits have been scheduled for this study, including Visit 1/screening period (Week -4), Visit 2/baseline (Week 0), Visit 3 (Week 1), Visit 4 (Week 2), Visit 5 (Week 3), Visit 6 (Week 4), Visit 7 (Week 8) and Visit 8 (Week 12).

A total of 300 subjects will participate in this study at 6 to 8 centers in China, and patient enrollment is expected to take up to 12 months.

Inclusion Criteria:

1. Adult Chinese subjects, at age≥18, either gender, diagnosed with osteoarthritis of the target knee and Kellgren-Lawrence (KL) classification Grade 1~3, as evidenced by X-ray examination in the last 3 months (mild to moderate narrowing of joint space and / or marked osteophytes of tibiofemoral joint space)
2. Persist pain of the target knee after exercise, weight loss and physical therapy;
3. A baseline WOMAC A1 score for the target knee rated at 40-90mm (moderate to severe walk-associated pain) on 100mm Visual analogue scale(VAS); Able to understand and sign the Informed Consent Form (ICF) that has already been approved by the Independent Ethics Committee (IEC) Note: the informed consent may also be given by the duly authorized representative of the subject.

Exclusion Criteria:

1. A diagnosis of bilateral knee osteoarthritis;
2. Clinically significant (requiring surgery) valgus or varus deformity of the knee joint, ligamentous laxity or unstable meniscus;
3. Complicated by inflammation or any other disease /condition (e.g., rheumatic arthritis, metabolic bone disease, psoriasis, gout, pseudogout, chondrocalcinosis, etc.) that may affect the knee joint;
4. A history of septicemia, clinically considered sub-acute infection of the target knee joint;
5. A history of surgery on the target knee (in the last 6 months);
6. A history of asthma, urticaria or allergy after use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs);
7. Severe hepatic or renal disease or hepatic /renal failure;
8. Any unscheduled surgery on the lower limb;
9. Clinically significant lower venous or lymphatic obstruction;
10. Clinically significant obvious exudation or inflammation of the target knee;
11. Skin disorders or infection at the injection site;
12. Pregnant or lactating women;
13. Known allergy to guanylin and / or any active ingredient or excipient of hyaluronic acid-based injection / diclofenac sodium;
14. Treatment with any hyaluronic acid (HA) or its derivatives for the target knee within six months before this trial;
15. Intra-articular (IA) injection of steroids into the target knee within 3 months before this trial;
16. Presence of any contraindication to IA injection, e.g., patients who are receiving anti-coagulation therapy or clinically have potential coagulation disorders (e.g., hepatic disease);
17. Presence of any clinically significant disease (e.g., significant mental or nervous disorders, alcohol/drug abuse), unstable/poorly controlled diseases, or other factors, which may affect their evaluation or participation in this study in the investigator's judgment
18. Perioperative pain associated with coronary artery bypass surgery (CABG);
19. A history of gastrointestinal bleeding or perforation following use of NSAIDs;
20. Presence of active gastrointestinal ulcer /bleeding, or a past history of recurrent ulcer/bleeding; Chief complaint complicated by pain beyond the target knee,