The long non-coding RNA HLA complex P5 (HCP5) is extensively related to cancer chemoresistance, while its function in gastric cancer (GC) has not been well elucidated yet. Here, the role and mechanism of HCP5 in regulating the chemoresistance of GC to cisplatin (DDP) was investigated. Our results revealed that HCP5 was increased in GC patients and indicated a poor prognosis. HCP5 knockdown weakens DDP resistance and reduced apoptosis of GC cells. miR-128 was decreased in GC patients and sponged by HCP5. HMGA2 was targeted by miR-128 and was increased in GC patients. HCP5 aggravated the resistance of GC cells to DDP in vitro by elevating HMGA2 expression via sponging miR-128. HCP5 silencing inhibited GC cells growth, resistance to DDP, and Ki-67 expression in vivo. In summary, HCP5 contributed to DDP resistance in GC cells through miR-128/HMGA2 axis, providing a promising therapeutic target for GC chemoresistance.