Tctex1 is an important element of the dynein motor unit in mammalian cells that helps move targets along microtubules and toward the centrosome for degradation. Here, we analyzed the role of Tctex1 in the α-synuclein autophagy-lysosome degradation pathway using Tctex1-siRNA in SH-SY5Y cells. Results showed that siRNA silencing of Tctex1 suppressed cellular viability and promoted cell apoptosis. Protein and mRNA expression of Tctex1 and dynein decreased after Tctex1 knockdown, whereas α-synuclein, LC3-II, and LAMP2 increased. Consistently, fluorescence intensity of Tctex1 was weaker in siRNA-Tctex1-transfected cells, and that of α-synuclein, LC3-II, and LAMP2 was increased. Tctex1 inhibition reduced cell viability and promoted apoptosis. These results show that Tctex1 plays an important role in α-synuclein autophagic degradation and in maintaining cellular homeostasis.