Objective: To investigate the effects of RNPC1 on the sensitivity of breast cancer cell MCF-7 with doxorubicin (DOX). Methods: Lentivirus was used to over-express and knock-down RNPC1 in the MCF-7 breast cancer cells. The cells were divided into overexpress RNPC1(RNPC1) group and its control(NC group), knock-down RNPC1(shRNPC1 group) and its control(SCR group). The relative mRNA and protein expression of RNPC1 was detected by qRT-PCR and Western blot, respectively. The experimental groups were treated with different concentration of DOX, and cell growth inhibition rate was tested cell counting kit 8(CCK-8). After the experimental groups was treated with DOX, cell apoptosis rate was analysis by flow cytometer assay and the expression of apoptosis-related protein was detected by Western blot assay. Results: The qRT-PCR and Western blot results showed that the mRNA and protein level of RNPC1 was increased after transfection with RNPC1 overexpression(RNPC1). While, RNPC1 was reduced after transfection with knockdown RNPC1 (shRNPC1) lentivirus. After treatment with different concentration of DOX, the IC50 of shRNPC1 group was significantly lower than SCR group (P <0.05). Furthermore, the IC50 of RNPC1 group was higher than NC group (P<0.05). The flow cytometer assay was used after treatment with DOX for 24 h in the experimental groups. The cell apoptosis rate of shRNPC1 group was higher than SCR group, while, the cell apoptosis rate of RNPC1 was lower than NC group. Overexpression of RNPC1 increased the expression of BCL-XL and BCL-2 after treatment with DOX. Reversely, knockdown of RNPC1 reduced the expression of BCL-XL and BCL-2. Furthermore, overexpression of RNPC1 reduced the expression of BIM and BID after treatment with DOX. While, knockdown of RNPC1 increased the expression of BIM and BID. Conclusion: RNPC1 could decrease the sensitivity of breast cancer cell MCF-7 to DOX, and the underlying mechanism might be related to cell apoptosis.