To this day, the inter-core crosstalk and intra-core crosstalk are potential factors limiting optical fiber transmission over long distances and serious degradation of signal quality in communication systems of multi-core few-mode fibers. To this end, this work proposes a heterogeneous sixteen-core four-mode fiber with two types of refractive index profiles is proposed in this paper, which consists of a graded-index core and a step-index core. After optimization, the four modes can transmit independently and steadily at 1550 nm, and the effective refractive index difference between adjacent modes is more than 1 × 10−3. Under the optimal fiber parameters, the inter-core crosstalk results can be obtained from the research results and are less than −69 dB/km, which reflects the significant effect of the proposed fiber in reducing the inter-core crosstalk. The proposed fiber is the first to use the combination of step-index core and graded-index core so that the inter-core crosstalk of heterogeneous fibers is successfully suppressed at a low level, while providing new ideas and solutions for future research on novel low-crosstalk multi-core few-mode fibers that can be applied to terrestrial and undersea communication systems.