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PURPOSE This study aimed to study the effect of long non-coding RNA (lncRNA) H19 on proliferation, apoptosis and chemosensitivity of nasopharyngeal carcinoma (NPC) cells. METHODS NP69 and HNE3, C666-1, SUNE1, 6-10B and 5-8F cell lines were selected to detect the expression of lncRNA H19 via RT-qPCR. LncRNA H19 was overexpressed or silenced for exploring the regulatory effect of lncRNA H19 in cell proliferation, clone formation, apoptosis and drug resistance through CCK-8, clone formation experiment and flow cytometry respectively. The tumorigenic effect of lncRNA H19 silencing was verified by xenograft tumor in nude mice. LncRNA H19 was significantly up-regulated in NPC cells. RESULTS Silencing lncRNA H19 inhibited the proliferation of NPC C666-1 cells and promoted apoptosis, while overexpression of lncRNA H19 promoted the proliferation of NPC C666-1 cells and inhibited apoptosis. Knockdown of lncRNA H19 in drug-resistant cells remarkably reduced their drug resistance, and overexpression of lncRNA H19 in parental cells significantly reduced their drug sensitivity. Silencing lncRNA H19 inhibits tumor growth in vivo, and silencing lncRNA H19 combined with paclitaxel can enhance tumor inhibition in vivo. CONCLUSIONS In NPC cells, lncRNA H19 was up-regulated, lncRNA H19 inhibited the proliferation and chemosensitivity of NPC cells, promoted apoptosis, and silencing lncRNA H19 combined with paclitaxel could enhance tumor inhibition in vivo.