Although the innovation factor endowment of Heilongjiang province is relatively rich, many innovation resources cannot effectively promote the sustainable development of innovation-driven performance. The combined drift degree evaluation method and grey-DEMATEL model were used to study regional innovation performance in Heilongjiang province and the key factors influencing it. The results of this study show that the overall trend of regional innovation performance is slowly rising. Compared with other regions, the level of science and technology output is in the forefront, and the level of economic output and social effect is at the end. The innovation performance level of enterprises and research institutions is at the end position, showing a trend of slow rise and then slow decline. The innovation performance level of universities is in the middle position, showing a trend of rising first, then falling and then rising. The degree of marketization, the financial environment, the intellectual property system, the transformation of scientific and technological achievements and the level of human capital are the core factors that affect the regional innovation performance. The dominant position and leading role of regional enterprises and the cooperation between industry, university and research institutes should be strengthened through government policies.