Objective To observe the expression difference of lncRNA FAL1 in ovarian cancer cells and their drug-resistant cell lines, and to explore the effect and mechanism of lncRNA FAL1 down-regulation on cell chemotherapy resistance. Methods The expression levels of fal1 gene in SKOV3 and COC1 cells and their drug-resistant cell lines were detected by qRT-PCR. fal1 siRNA was transfected to downregulate fal1 gene expression. MTT was used to detect cell proliferation. Transwell method was used to detect cell invasion ability. Plate clone formation test was used to detect cell clone ability, and Western blot was used to detect MDR-1, mpr-1, ABCG2 and phosphorylation levels of p38 MAPK, ERK1/2 and JNK. SKOV3/DDP and COC1/DDP cells transfected with FAL1-siRNA were injected subcutaneously into BALB/c nude mice. The volume and mass of subcutaneous transplanted tumors were measured. Results Compared with SKOV3 and COC1 cells, SKOV3/DDP and COC1/DDP cells were less sensitive to DDP, and the expression levels of FAL1 gene increased (P < 0.01). After transfection with FAL1-siRNA, the sensitivity of SKOV3/DDP and COC1/DDP cells to DDP increased (P < 0.01), and the invasion (P < 0.05) and cloning ability (P < 0.01) decreased. The expression levels of MDR-1, MPR-1, ABCG2 (P < 0.01) and the phosphorylation levels of p38 MAPK, ERK1/2 and JNK (P < 0.05) decreased. The volume and mass of subcutaneous transplanted tumors were significantly reduced (P < 0.01). Conclusion Down-regulation of lncRNA FAL1 could significantly reduce the chemotherapy resistance of cisplatin-resistant ovarian cancer cell lines and inhibit the proliferation of drug-resistant cells in vivo. Its mechanism is related to inhibiting the activation of MAPK signaling pathway.