Multiplication is an essential biomedical signal processing function implemented in the Digital Signal Processing (DSP) cores. To enhance the speed, area and energy efficiency of DSP cores, approximate multiplication is used. Also, low power multiplier unit design is one of the requirements of DSP processor to meet the increasing demands. To balance both the design and error metrics of a multiplier design, an efficient Hybrid Radix-16 Booth Encoding and rounding-based approximate Karatsuba Multiplier (RBEKM-16) is proposed. This research introduces an Approximate Karatsuba multiplier based on rounding, utilizing rounding approximation to compute the least significant part of the product. Simple operators, like adders and multiplexers, replace complex and costly conventional Floating-Point (FP) multipliers in this process. Radix-4 logarithms are incorporated to further minimize hardware complexity and calculate the product's most significant part. Subsequently, an approximate 4-2 compressor is applied in the partial product reduction stage to generate the most significant bit result. In the experimental scenario, the efficiency of the multiplier is evaluated in terms of energy efficiency, area utilization and error rate by using Xilinx ISE 8.1i tool. The results from the experiments indicate that the suggested multiplier demonstrates improved energy efficiency, utilizes space more effectively, and performs well in applications related to biomedical signal processing. Further, the accomplished area utilization of the proposed 16-bit multiplier is 1068 μm2, delay is 3.01 ns, power consumption is 0.021 mW and power delay product is 119 fJ.